Search results for: red blood cells

Authors: Dylan Santos De Pinho, Arnaud Gay De Combes, Matthieu Steuhlet, Claude Jeannerat, Nabil Ouerhani

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The Industry 4.0 initiative has been launched to address huge challenges related to ever-smaller batch sizes. The end-user need for highly customized products requires highly adaptive production systems in order to keep the same efficiency of shop floors. Most of the classical Software solutions that operate the manufacturing processes in a shop floor are based on rigid Manufacturing Execution Systems (MES), which are not capable to adapt the production order on the fly depending on changing demands and or conditions. In this paper, we present a highly modular and flexible solution to orchestrate a set of production systems composed of a micro-milling machine-tool, a polishing station, a cleaning station, a part inspection station, and a rough material store. The different stations are installed according to a novel matrix configuration of a 3x3 vertical shelf. The different cells of the shelf are connected through horizontal and vertical rails on which a set of shuttles circulate to transport the machined parts from a station to another. Our software solution for orchestrating the tasks of each station is based on a Multi-Agent System. Each station and each shuttle is operated by an autonomous agent. All agents communicate with a central agent that holds all the information about the manufacturing order. The core innovation of this paper lies in the path planning of the different shuttles with two major objectives: 1) reduce the waiting time of stations and thus reduce the cycle time of the entire part, and 2) reduce the disturbances like vibration generated by the shuttles, which highly impacts the manufacturing process and thus the quality of the final part. Simulation results show that the cycle time of the parts is reduced by up to 50% compared with MES operated linear production lines while the disturbance is systematically avoided for the critical stations like the milling machine-tool.

Keywords: multi-agent systems, micro-manufacturing, flexible manufacturing, transfer systems

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Authors: Héctor González Espinosa, Ricardo Ivan Cordova Chávez, Alejandra Contreras Ramos, Itzia Irene Padilla Martínez, José Guadalupe Trujillo Ferrara, Marvin Antonio Soriano Ursúa

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Boronic acids are able to create diester bonds with carbohydrates because of their hydroxyl groups; in nature, there are some organoborates with these characteristics, such as the calcium fructoborate, formed by the union of two fructose molecules and a boron atom, synthesized by plants. In addition, it has been observed that, in animal cells only the compounds with cis-diol functional groups are capable of linking to boric or boronic acids. The formation of these organoboron compounds could impair the physical and chemical properties of the precursors, even their acute toxicity. In this project, two carbohydrate-derived boron-containing compounds from D-fructose and D-arabinose and phenylboronic acid are analyzed by different spectroscopy techniques such as Raman, Infrared with Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) and X-ray diffraction crystallography to describe their chemical characteristics. Also, an acute toxicity test was performed to determine their LD50 using the Lorke’s method. It was confirmed by multiple spectra the formation of the adducts by the generation of the diester bonds with a β-D-pyranose of fructose and arabinose. The most prominent findings were the presence of signals corresponding to the formation of new bonds, like the stretching of B-O bonds, or the absence of signals of functional groups like the hydroxyls presented in the reagents used for the synthesis of the adducts. The NMR spectra yielded information about the stereoselectivity in the synthesis reaction, observed by the interaction of the protons and their vicinal atoms in the anomeric and second position carbons; but also, the absence of a racemic mix by the finding of just one signal in the range for the anomeric carbon in the 13C NMR spectra of both adducts. The acute toxicity tests by the Lorke’s method showed that the LD50 value for both compounds is 1265 mg/kg. Those results let us to propose these adducts as highly safe agents for further biological evaluation with medical purposes.

Keywords: acute toxicity, adduct, boron, carbohydrate, diester bond

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Authors: Navid P Roodaki, Rochelle Abila, Daisy Evangeline Garcia

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Background and Objective: Respiratory Distress Syndrome (RDS) among premature infants is a major causes of neonatal death. The use of Continuous Positive Airway Pressure (CPAP) has become a standard of care for preterm newborns with RDS hence cost-effective innovations are needed. This study compared a novel low-cost Bubble CPAP (bCPAP) device to ventilator driven CPAP in the treatment of RDS. Methods: This is a single-blind, randomized controlled trial done on May 2022 to October 2022 in a Level III Neonatal Intensive Care Unit in the Philippines. Preterm newborns (<36 weeks) with RDS were randomized to receive Vayu bCPAP device or Ventilator-derived CPAP. Arterial Blood Gases, Oxygen Saturation, administration of surfactant, and CPAP failure rates were measured. Results: Seventy preterm newborns were included. No differences were observed between the Ventilator driven CPAP and Vayu bCPAP on the PaO2 (97.51mmHg vs 97.37mmHg), So2 (97.08% vs 95.60%) levels, amount of surfactant administered between groups. There were no observed differences in CPAP failure rates between Vayu bPCAP (x̄ 3.23 days) and ventilator-driven CPAP (x̄ 2.98 days). However, a significant difference was noted on the CO2 level (40.32mmHg vs 50.70mmHg), which was higher among those hooked to Ventilator-driven CPAP (p 0.004). Conclusion: This study has shown that the novel low-cost bubble CPAP (Vayu bCPAP) can be used as an efficacious alternate non invasive oxygen therapy among preterm neonates with RDS, although the CO2 levels were higher among those hooked to ventilator driven CPAP, other outcome parameters measured showed that both devices are comparable. Recommendation: A multi-center or national study to account for geographic region, which may alter the outcomes of patients connected to different ventilatory support. Cost comparison between devices is also suggested. A mixed-method research assessing the experiences of health care professionals in assembling and utilizing the gadget is a second consideration.

Keywords: bubble CPAP, ventilator-derived CPAP; infant, premature, respiratory distress syndrome

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Authors: Girgis Younan, Ikram Eltayeb

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Geigeria alata belongs to the family Asteraceae, is an effective plant traditionally used in Sudan as a therapy for hepatic disease and as an antiepileptic, antispasmodic and to treat cough and intestinal complaints.The liver is responsible for many critical functions within the body and any liver disease or injury will result in the loss of those functions leading to significant damage in the body. Liver diseases cause increase in liver enzymes (AST, ALP ALT) and total bilirubin and a decrease in total blood protein level. The objective of this study is to investigate the hepato-protective activity of Geigeria alata leaves ethanolic extract. The plant leaves were extracted using 96% ethanol using Soxhlet apparatus. The hepatoprotective effect was determined using 25 wistar rats, the rats was divided to 5 groups, each group contain 5 rats: [Normal control group] receiving purified water, liver damage was induced in wistar rats by administering a 1:1 (v/v) mixture of CCl4 (1.25 ml/kg) and olive oil once at day four of the experiment [negative control group]. Two doses of extract [400mg/kg and 200mg/kg] was applied daily for 7 days, and standard drug Silymarin (200 mg/kg) were administered daily for 7 days to CCl4-treated rats. The degree of hepato-protective activity was evaluated by determining the hepatic marker enzymes AST, ALP, ALT, total Bilirubin and total proteins (TP). Results have shown that, the extract of G.alata leaves reduced the level of liver enzymes ALT, AST, ALP, total bilirubin and increased the level of total proteins. Since the levels of liver enzymes; bilirubin and total protein are considered as markers of liver function, the extract has proven to reduce the detrimental effects of liver toxicity induced using CCl4. The hepato-protective effect of extract on liver was found to be dose dependent, where the 400mg/kg dose of the extract exhibited higher activity than 200mg/kg dose. In addition, the effect of the higher dose (400mg/kg) of the extract was found to be higher than Silymarin standard drug. The result concludes that, G.alata leaves extract was found to exhibit profound hepato-protective activity, which justifies the traditional use of the plant for the treatment of hepatic diseases.

Keywords: alata, extract, geigeria, hepatoprotective

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Authors: Osama Moustafa Zayed

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Aim of the work: To evaluate the effectiveness of venous glucose, levels of serum lactate and base deficit in polytraumatized patients as simple parameters to predict the mortality in these patients. Compared to the predictive value of Trauma and injury severity (TRISS) and Acute Physiology And Chronic Health Evaluation IV (APACHE IV). Introduction: Trauma is a serious global health problem, accounting for approximately one in 10 deaths worldwide. Trauma accounts for 5 million deaths per year. Prediction of mortality in trauma patients is an important part of trauma care. Several trauma scores have been devised to predict injury severity and risk of mortality. The trauma and injury severity score (TRISS) was most common used. Regardless of the accuracy of trauma scores, is based on an anatomical description of every injury and cannot be assigned to the patients until a full diagnostic procedure has been performed. So we hypothesized that alterations in admission glucose, lactate levels and base deficit would be an early and easy rapid predictor of mortality. Patient and Method: a comparative cross-sectional study. 282 Polytraumatized patients attended to the Emergency Department(ED) of the Suez Canal university Hospital constituted. The period from 1/1/2012 to 1/4/2013 was included. Results: We found that the best cut off value of TRISS probability of survival score for prediction of mortality among poly-traumatized patients is = 90, with 77% sensitivity and 89% specificity using area under the ROC curve (0.89) at (95%CI). APACHE IV demonstrated 67% sensitivity and 95% specificity at 95% CI at cut off point 99. The best cutoff value of Random Blood Sugar (RBS) for prediction of mortality was>140 mg/dl, with 89%, sensitivity, 49% specificity. The best cut off value of base deficit for prediction of mortality was less than -5.6 with 64% sensitivity, 93% specificity. The best cutoff point of lactate for prediction of mortality was > 2.6 mmol/L with 92%, sensitivity, 42% specificity. Conclusion: According to our results from all evaluated predictors of mortality (laboratory and scores) and mortality based on the estimated cutoff values using ROC curves analysis, the highest risk of mortality was found using a cutoff value of 90 in TRISS score while with laboratory parameters the highest risk of mortality was with serum lactate > 2.6 . Although that all of the three parameter are accurate in predicting mortality in poly-traumatized patients and near with each other, as in serum lactate the area under the curve 0.82, in BD 0.79 and 0.77 in RBS.

Keywords: APACHE IV, emergency department, polytraumatized patients, serum lactate

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Authors: Bashair Al Riyami

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Background: Acylation stimulating protein (ASP) is a small basic protein that was isolated based on its function as a potent lipogenic factor. The role of ASP in lipid metabolism has been described in numerous studies. Several association studies suggest that ASP may play a prominent role in female fat metabolism and distribution. Progesterone is established as a female lipogenic hormone, however the mechanisms by which progesterone exert its effects are not fully understood. AIM: Since ASP is an established potent lipogenic factor with a known mechanism of action, in this study we aim to investigate acute effects of different hormone treatments on ASP levels in vivo after a fat load. Methods: This is a longitudinal study including 24 female wister rats that were randomly divided into 4 groups including controls (n=6). The rats were ovariectomized, and fourteen days later the fasting rats were injected subcutaneously with a single dose of different hormone treatments (progesterone, estrogen and testosterone). An hour later, olive was administered by oral gavage, and plasma blood samples were collected at several time points after oil administration for ASP and triglyceride measurements. Area under the curve (TG-AUC) was calculated to represent TG clearance Results: RM-ANCOVA and post-analysis showed that only the progesterone treated group had a significant postprandial ASP increase at two hours compared to basal levels and to the controls (439.8± 62.4 vs 253.45± 59.03 ug/ml), P= 0.04. Interestingly, increased postprandial ASP levels coordinated negatively with corresponding TG levels and TG-AUC across the postprandial period most apparent in the progesterone and testosterone treated groups that behaved in an opposite manner. ASP levels were 3-fold higher in the progesterone compared to the testosterone treated group, whereas TG-AUC was significantly lower in the progesterone treated group compared to the testosterone treated group. Conclusion: These findings suggest that progesterone treatment enhances ASP production and TG clearance in a simultaneous manner. The strong association of postprandial ASP levels and TG clearance in the progesterone treated group support the notion of a stimulatory role for progesterone on ASP mediated TG clearance. This is the first functional study to demonstrate a cause-effect relationship between hormone treatment and ASP levels in vivo. These findings are promising and may contribute to further understanding the mechanism of progesterone function as a female lipogenic hormone through enhancing ASP production and plasma levels.

Keywords: ASP, lipids, sex hormones, wister rats

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Authors: Asrat Agalu Abejew

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Background: Antimicrobial resistance (AMR) is a silent tsunami and one of the top global threats to health care and public health. It is one of the common agendas globally and in Ethiopia. Emerging AMR will be a double burden to Ethiopia, which is facing a series of problems from infectious disease morbidity and mortality. In Ethiopia, although there are attempts to document AMR in healthcare institutions, comprehensive and all-inclusive analysis is still lacking. Thus, this study is aimed to determine trends in AMR from 2016-2021. Methods: A retrospective analysis of secondary data recorded in the Amhara Public Health Institute (APHI) from 2016 to 2021 G.C was conducted. Blood, Urine, Stool, Swabs, Discharge, body effusions, and other Microbiological specimens were collected from each study participants, and Bacteria identification and Resistance tests were done using the standard microbiologic procedure. Data was extracted from excel in August 2022, Trends in AMR were analyzed, and the results were described. In addition, the chi-square (X2) test and binary logistic regression were used, and a P. value < 0.05 was used to determine a significant association. Results: During 6 years period, there were 25143 culture and susceptibility tests. Overall, 265 (46.2%) bacteria were resistant to 2-4 antibiotics, 253 (44.2%) to 5-7 antibiotics, and 56 (9.7%) to >=8 antibiotics. The gram-negative bacteria were 166 (43.9%), 155 (41.5%), and 55 (14.6%) resistant to 2-4, 5-7, and ≥8 antibiotics, respectively, whereas 99(50.8%), 96(49.2% and 1 (0.5%) of gram-positive bacteria were resistant to 2-4, 5-7 and ≥8 antibiotics respectively. K. pneumonia 3783 (15.67%) and E. coli 3199 (13.25%) were the most commonly isolated bacteria, and the overall prevalence of AMR was 2605 (59.9%), where K. pneumonia 743 (80.24%), E. cloacae 196 (74.81%), A. baumannii 213 (66.56%) being the most common resistant bacteria for antibiotics tested. Except for a slight decline during 2020 (6469 (25.4%)), the overall trend of AMR is rising from year to year, with a peak in 2019 (8480 (33.7%)) and in 2021 (7508 (29.9%). If left un-intervened, the trend in AMR will increase by 78% of variation from the study period, as explained by the differences in years (R2=0.7799). Ampicillin, Augmentin, ciprofloxacin, cotrimoxazole, tetracycline, and Tobramycin were almost resistant to common bacteria they were tested. Conclusion: AMR is linearly increasing during the last 6 years. If left as it is without appropriate intervention after 15 years (2030 E.C), AMR will increase by 338.7%. A growing number of multi-drug resistant bacteria is an alarm to awake policymakers and those who do have the concern to intervene before it is too late. This calls for a periodic, integrated, and continuous system to determine the prevalence of AMR in commonly used antibiotics.

Keywords: AMR, trend, pattern, MDR

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Authors: Hansraj Riteesh Bookun, Cassandra Monique Hidajat

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This pilot study investigated the efficacy of a newly designed shoe which will act as an intermittent pneumatic compression device to augment venous flow in the lower limb. The aim was to assess the degree with which a wearable intermittent compression device can increase the venous flow in the popliteal vein. Background: Deep venous thrombosis and chronic venous insufficiency are relatively common problems with significant morbidity and mortality. While mechanical and chemical thromboprophylaxis measures are in place in hospital environments (in the form of TED stockings, intermittent pneumatic compression devices, analgesia, antiplatelet and anticoagulant agents), there are limited options in a community setting. Additionally, many individuals are poorly tolerant of graduated compression stockings due to the difficulty in putting them on, their constant tightness and increased associated discomfort in warm weather. These factors may hinder the management of their chronic venous insufficiency. Method: The device is lightweight, easy to wear and comfortable, with a self-contained power source. It features a Bluetooth transmitter and can be controlled with a smartphone. It is externally almost indistinguishable from a normal shoe. During activation, two bladders are inflated -one overlying the metatarsal heads and the second at the pedal arch. The resulting cyclical increase in pressure squeezes blood into the deep venous system. This will decrease periods of stasis and potentially reduce the risk of deep venous thrombosis. The shoe was fitted to 2 healthy participants and the peak systolic velocity of flow in the popliteal vein was measured during and prior to intermittent compression phases. Assessments of total flow volume were also performed. All haemodynamic assessments were performed with ultrasound by a licensed sonographer. Results: Mean peak systolic velocity of 3.5 cm/s with standard deviation of 1.3 cm/s were obtained. There was a three fold increase in mean peak systolic velocity and five fold increase in total flow volume. Conclusion: The device augments venous flow in the leg significantly. This may contribute to lowered thromboembolic risk during periods of prolonged travel or immobility. This device may also serve as an adjunct in the treatment of chronic venous insufficiency. The study will be replicated on a larger scale in a multi—centre trial.

Keywords: venous, intermittent compression, shoe, wearable device

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Authors: Roya Bakhtiar, Alireza Abdolmohammadi, Hadi Hajarian, Zahra Nikousefat, Davood, Kalantar-Neyestanaki

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The objective of the present study was to determine the polymorphism in the leptin (332G>A) and its association with biometric traits in Sanjabi sheep. For this purpose, blood samples from 96 rams were taken, and tail length, width tail, circumference tail, body length, body width, and height were simultaneously recorded. PCR was performed using specific primer to amplify 463 bp fragment including exon 3 of leptin gene, and PCR products were digested by Cail restriction enzymes. The 332G>A (at 332th nucleotide of exon 3 leptin gene) that caused an amino acid change from Arg to Gln was detected by Cail (CAGNNNCTG) endonuclease, as the endonuclease cannot cut this region if G nucleotide is located in this position. Three genotypes including GG (463), GA (463, 360and 103 bp) and GG (360 bp and 103 bp) were identified after digestion by enzyme. The estimated frequencies of three genotypes including GG, GA, and AA for 332G>A locus were 0.68, 0.29 and 0.03 and those were 0.18 and 0.82 for A and G alleles, respectively. In the current study, chi-square test indicated that 332G>A positions did not deviate from the Hardy–Weinberg (HW) equilibrium. The most important reason to show HW equation was that samples used in this study belong to three large local herds with a traditional breeding system having random mating and without selection. Shannon index amount was calculated which represent an average genetic variation in Sanjabi rams. Also, heterozygosity estimated by Nei index indicated that genetic diversity of mutation in the leptin gene is moderate. Leptin gene polymorphism in the 332G>A had significant effect on body length (P<0.05) trait, and individuals with GA genotype had significantly the higher body length compared to other individuals. Although animals with GA genotype had higher body width, this difference was not statistically significant (P>0.05). This non-synonymous SNP resulted in different amino acid changes at codon positions111(R/Q). As leptin activity is localized, at least in part, in domains between amino acid residues 106-1406, it is speculated that the detected SNP at position 332 may affect the activity of leptin and may lead to different biological functions. Based to our results, due to significant effect of leptin gene polymorphism on body size traits, this gene may be used a candidate gene for improving these traits.

Keywords: body size, Leptin gene, PCR-RFLP, Sanjabi sheep

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Authors: T. Rakhi, Thrivikram Shenoy

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Esophageal atresia is a disorder of maldevelopment of esophagus with or without a connection to the trachea. Radiological reviews are needed in consultation with the pediatric surgeon and neonatologist and we report a rare case of esophageal atresia associated with atrial septal defect-patent ductus arteriosus complex. A 2-day old female baby born at term, weighing 3.010kg, admitted to the Neonatal Intensive Care Unit with respiratory distress and excessive oral secretions. On examination, continuous murmur and cyanosis were seen. Esophageal atresia was suspected, after a failed attempt to pass a nasogastric tube. Chest radiograph showed coiling of the nasogastric tube and absent gas shadow in the abdomen. Echocardiography confirmed Patent Ductus Arteriosus with Atrial Septal Defect not in failure and was diagnosed with esophageal atresia with suspected fistula posted for surgical repair. After preliminary management with oxygenation, suctioning in prone position and antibiotics, investigations revealed Hb 17gms serum biochemistry, coagulation profile and C-Reactive Protein Test normal. The baby was premedicated with 5mcg of fentanyl and 100 mcg of midazolam and a rapid awake laryngoscopy was done to rule out difficult airway followed by induction with o2 air, sevo and atracurium 2 mg. Placement of a 3.5 tube was uneventful at first attempt and after confirming bilateral air entry positioned in the lateral position for Right thoracotomy. A pulse oximeter, Echocardiogram, Non-invasive Blood Pressure, temperature and a precordial stethoscope in left axilla were essential monitors. During thoracotomy, both the ends of the esophagus and the fistula could not be located after thorough search suggesting an on table finding of type A esophageal atresia. The baby was repositioned for gastrostomy, and cervical esophagostomy ventilated overnight and extubated uneventful. Absent gas shadow was overlooked and the purpose of this presentation is to create an awareness between the neonatologist, pediatric surgeons and anesthesiologist regarding variation of typing of Tracheoesophageal fistula pre and intraoperatively. A need for imaging modalities warranted for a definitive diagnosis in the presence of a gasless stomach.

Keywords: anesthetic, atrial septal defects, esophageal atresia, patent ductus arteriosus, perioperative, chest x-ray

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Authors: Yunjia Yang, Yakun Yan, Peng Li, Gordon Xu, Timothy Mahony, Neena Mitter, Karishma Mody

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Sheep flystrike is one of the most economically important diseases affecting the Australian sheep and wool industry (>356M/annually). Currently, control of Lucillia cuprina relies almost exclusively on chemicals controls and the parasite has developed resistance to nearly all control chemicals used in the past. It is therefore critical to develop an alternative solution for the sustainable control and management of flystrike. RNA interference (RNAi) technologies have been successfully explored in multiple animal industries for developing parasites controls. This research project aims to develop a RNAi based biological control for sheep blowfly. Double-stranded RNA (dsRNA) has already proven successful against viruses, fungi and insects. However, the environmental instability of dsRNA is a major bottleneck with a protection window only lasting 5-7 days. Bentonite polymer (BenPol) technology can overcome this problem, as it can be tuned for controlled release of the dsRNA in the gut challenging pH environment of the blowfly larvae, prolonging its exposure time to and uptake by target cells. We have investigated four different BenPol carriers for their dsRNA loading capabilities of which three of them were able to afford dsRNA stability under multiple temperatures (4°C, 22°C, 40°C, 55°C) in the sheep serum. Based on stability results, we further tested dsRNA from potential targeted genes loaded with BenPol carrier in larvae feeding assay, and get three knockdowns. Our results, establish that the dsRNA when loaded on BenPol particles is stable unlike naked dsRNA which is rapidly degraded in the sheep serum. A stable nanoparticles delivery system that can protect and increase the inherent stability of the dsRNA molecules at higher temperatures in a complex biological fluid like serum, offers a great deal of promise for the future use of this approach for enhancing animal protection.

Keywords: RNA interference, Lucillia cuprina, polymer carriers, polymer stability

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Authors: Amina Aloui, Jalila Ben Salah-Abbès, Abdellah Zinedine, Amar Riba, Noel Durand, Catherine Brabet, Didier Montet, Samir Abbès

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Mycotoxin contamination of food and feed-isa globaconcern, both economically and for public health. Aflatoxin M1 (AFM1) is the principal hydroxylated metabolite of aflatoxin B1. It is frequently found in milk and other dairy products. It is responsible for the development of hepatocellular carcinoma and immunotoxic in humans and animals. The reduction of its bioavailabilitybecomesa great demand in order to protect human and animal health. The use of probiotic bacteria and clay are demonstrated to be able to bind AFM1 in vitro. This study aimed to investigate, in vivo, the activity of two-component mixture: L. rhamnosusGAF06 (LR) and bentonite for reducing the oxidative stress and the histological alterationsinduced by AFM1 in the liver andkidneys. For the experiment, male mice were divided into 7 groups (6 mice/group) and treated, orally, by AFM1, alone or in combination with LR and/or bentonite, for 10 days as follows: group 1 control, group 2 treated with LR alone (2.108 CFU/ml), group 3 treated with bentonite alone (1g/kg), group 4 treated with AFM1 alone (100μg/kg), group 5 co-treated with LR+AFM1, group 6 co-treated with bentonite+AFM1, group 7 co-treated with bentonite+LR+AFM1. At the end of the treatment, the mice were sacrificed, and the livers and kidneys were collected for histological assays. Intracellular antioxidant activities and lipid peroxidation were also studied. The results showed that AFM1causeddamage in liver and kidney tissues, being evidence of hepatotoxicity and nephrotoxicity marked by necrotic cells. It increased the MDA level and decreased the antioxidant enzyme activities (SOD) in both organs. In contrast, the co-treatment with AFM1 plus LR and/or bentonitesignificantly improved the hepatic and renal tissues, regulated kidney, and liver antioxidant enzyme activities. This improvement was more remarkable with the administration of LR-bentonite mixture with AFM1.LR and bentonite alone showed to be safe during the treatment. This mixture can be a promising candidate for future applications in biotechnological processes that aimed to detoxify AFM1in food and feed.

Keywords: aflatoxin M1, bentonite, L. rhamnosus GAF06, oxidative stress, prevention

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Authors: Hamsa T. Tayeb, Mohammad A. Arafah, Dana M. Bakheet, Duaa M. Khalaf, Agnieszka Tarnoska, Nduna Dzimiri

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Background: CYP2D6 is a member of the cytochrome P450 mixed-function oxidase system. The enzyme is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, especially in breast cancer and psychiatric therapy. Different phenotypes have been described displaying alleles that lead to a complete loss of enzyme activity, reduced function (poor metabolizers – PM), hyperfunctionality (ultrarapid metabolizers–UM) and therefore drug intoxication or loss of drug effect. The prevalence of these variants may vary among different ethnic groups. Furthermore, the xTAG system has been developed to categorized all patients into different groups based on their CYP2D6 substrate metabolization. Aim of the study: To determine the prevalence of the different CYP2D6 variants in our population, and to evaluate their clinical relevance in personalized medicine. Methodology: We used the Luminex xMAP genotyping system to sequence 305 Saudi individuals visiting the Blood Bank of our Institution and determine which polymorphisms of CYP2D6 gene are prevalent in our region. Results: xTAG genotyping showed that 36.72% (112 out of 305 individuals) carried the CYP2D6_*2. Out of the 112 individuals with the *2 SNP, 6.23% had multiple copies of *2 SNP (19 individuals out of 305 individuals), resulting in an UM phenotype. About 33.44% carried the CYP2D6_*41, which leads to decreased activity of the CYP2D6 enzyme. 19.67% had the wild-type alleles and thus had normal enzyme function. Furthermore, 15.74% carried the CYP2D6_*4, which is the most common nonfunctional form of the CYP2D6 enzyme worldwide. 6.56% carried the CYP2D6_*17, resulting in decreased enzyme activity. Approximately 5.73% carried the CYP2D6_*10, consequently decreasing the enzyme activity, resulting in a PM phenotype. 2.30% carried the CYP2D6_*29, leading to decreased metabolic activity of the enzyme, and 2.30% carried the CYP2D6_*35, resulting in an UM phenotype, 1.64% had a whole-gene deletion CYP2D6_*5, thus resulting in the loss of CYP2D6 enzyme production, 0.66% carried the CYP2D6_*6 variant. One individual carried the CYP2D6_*3(B), producing an inactive form of the enzyme, which leads to decrease of enzyme activity, resulting in a PM phenotype. Finally, one individual carried the CYP2D6_*9, which decreases the enzyme activity. Conclusions: Our study demonstrates that different CYP2D6 variants are highly prevalent in ethnic Saudi Arabs. This finding sets a basis for informed genotyping for these variants in personalized medicine. The study also suggests that xTAG is an appropriate procedure for genotyping the CYP2D6 variants in personalized medicine.

Keywords: CYP2D6, hormonal breast cancer, pharmacogenetics, polymorphism, psychiatric treatment, Saudi population

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Authors: Benjawan Saengwichian, Alasdair E. Charles, Philip J. Hyde

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Magnetically controlled growing rods (MCGRs) have been used to stabilise and correct spinal curvature in children to support non-invasive scoliosis adjustment. Although the encapsulated driving components are intended to be isolated from body fluid contact, in vivo corrosion was observed on these components due to sealing mechanism damage. Consequently, a corrosion circuit is created with the body fluids, resulting in malfunction of the lengthening mechanism. Particularly, the chloride ions in blood plasma or cerebrospinal fluid (CSF) may corrode the MCGR alloys, possibly resulting in metal ion release in long-term use. However, there is no data available on the corrosion resistance of spinal implant alloys in CSF. In this study, an in vitro immersion configuration was designed to simulate in vivo corrosion of 440C SS-Ti6Al4V couples. The 440C stainless steel (SS) was heat-treated to investigate the effect of tempering temperature on intergranular corrosion (IGC), while crevice and galvanic corrosion were studied by limiting the clearance of dissimilar couples. Tests were carried out in a neutral artificial cerebrospinal fluid (ACSF) and phosphate-buffered saline (PBS) under aeration and deaeration for 2 months. The composition of the passive films and metal ion release were analysed. The effect of galvanic coupling, pH, dissolved oxygen and anion species on corrosion rates and corrosion mechanisms are discussed based on quantitative and qualitative measurements. The results suggest that ACSF is more aggressive than PBS due to the combination of aggressive chlorides and sulphate anions, while phosphate in PBS acts as an inhibitor to delay corrosion. The presence of Vivianite on the SS surface in PBS lowered the corrosion rate (CR) more than 5 times for aeration and nearly 2 times for deaeration, compared with ACSF. The CR of 440C is dependent on passive film properties varied by tempering temperature and anion species. Although the CR of Ti6Al4V is insignificant, it tends to release more Ti ions in deaerated ACSF than under aeration, about 6 µg/L. It seems the crevice-like design has more effect on macroscopic corrosion than combining the dissimilar couple, whereas IGC is dominantly observed on sensitized microstructure.

Keywords: cerebrospinal fluid, crevice corrosion, intergranular corrosion, magnetically controlled growing rods

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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: Anna-Mari Kok, Carel B. Oosthuizen, Namrita Lall

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Tuberculosis (TB) is a disease caused by the bacterial pathogen Mycobacterium tuberculosis. It is associated with high mortality rates in both developing and developed countries. Many higher plants are found that are medicinally associated with tuberculosis infection. Plants belonging to thirteen families were selected, based on their traditional usage for tuberculosis and its associated symptoms. Eight plants showed the best antimycobacterial activities (MIC-value ≤ 500.0 µg/ml) against M. tuberculosis H37Rv. LS was found to have a minimum inhibitory concentration (MIC) of 125 µg/ml whereas, Tulbaghia violacea, Heteromorpha arborescens, Sutherlandia frutescens, Eucalyptus deglupta, and Plectranthus neochilus were found to have a MIC value of 250 µg/ml against M. tuberculosis H37Rv. Cytotoxicity values on U937 and HepG2 cells were obtained and the IC50 values ranged between 40 ±4.30 and > 400 µg/ml for the U937 cell line and 72.4 ±1.50 and > 400 µg/ml for the HepG2 cell line. Heteromorpha arborescens had the lowest IC50 value in both cell lines and therefore showed moderate levels of toxicity. Of the 19 samples that underwent the 2, 2- diphenyl- 1- picrylhydrazyl (DPPH) antioxidant assay, Eucalyptus deglupta and Melianthus major showed significant free radical scavenging activities with concentrations of 1.33 and 1.32 µg/ml respectively for the inhibition of DPPH. Hepatotoxicity induced by acetaminophen identified Searsia lancea with hepatoprotective activity of 59.37% at a ¼ IC50 concentration. Out of the 7 samples that were investigated for their immunomodulatory capabilities, Eucalyptus deglupta produced the most IL-12 with Sutherlandia frutescens also showing positive results for IL-12 production. In the present study, Eucalyptus deglupta showed the most promising results with good activity against M. tuberculosis with an MIC-value of 250 µg/ml. It also has potent antioxidant activity with an IC50 value of 1.33 µg/ml. This sample also stimulated high production of the cytokine, IL-12. Searsia lancea showed moderate antimycobacterial acticvity with an MIC-value of 500 µg/ml. The antioxidant potential also showed promising results with an IC50 value of 4.50 µg/ml. The hepatoprotective capability of Searsia lancea was 59.34% at a ¼ IC50 concentration. Another sample Sutherlandia frutescens showed effective antimycobacterial activity with an MIC-value of 250 µg/ml. It also stimulated production of IL-12 with 13.43 pg/ml produced. These three samples can be considered for further studies for the consideration as adjuvants for current tuberculosis treatment.

Keywords: adjuvant, hepatoprotection, immunomodulation, tuberculosis

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Authors: D. Nagalakshmi, S. Parashuramulu K. Sadasiva Rao, G. Aruna, L. Vikram

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The zinc (Zn) is the second most abundant trace element in mammals and birds, forming structural component of over 300 enzymes, playing an important role in anti-oxidant defense, immune response and reproduction. Organic trace minerals are more readily absorbed from the digestive tract and more biologically available compared with its inorganic salt. Thus, the present study was undertaken on 60 adult female Sprague Dawley rats (275±2.04 g) for experimental duration of 12 weeks to investigate the effect of dietary Zn supplementation from various organic sources on immunity, reproduction, oxidative defense mechanism and blood biochemical profile. The rats were randomly allotted to 30 replicates (2 per replicate) which were in turn randomly allotted to 5 dietary treatments varying in Zn source i.e., one inorganic source (Zn carbonate) and 4 organic sources (Zn-proteinate, Zn-propionate, Zn-amino acid complex and Zn-methionine) so as to supply NRC recommended Zn concentration (12 ppm Zn). Supplementation of organic Zn had no effect on various haematological and serum biochemical constituents compared to inorganic Zn fed rats. The TBARS and protein carbonyls concentration in liver indicative of oxidative stress was comparable between various organic and inorganic groups. The glutathione reductase activity in haemolysate (P<0.05) and reduced glutathione concentration in liver (P<0.01) was higher when fed organic Zn and RBC catalase activity was higher (P<0.01) on Zn methionine compared to other organic sources tested and the inorganic source. The humoral immune response assessed as antibody titres against sheep RBC was higher (P<0.05) when fed organic sources of zinc compared to inorganic source. The cell mediated immune response expressed as delayed type hypersensitivity reaction was higher (P<0.05) in rats fed Zn propionate with no effect of other organic Zn sources. The serum progesterone concentration was higher (P<0.05) in rats fed organic Zn sources compared to inorganic zinc. The data on ovarian folliculogenesis indicated that organic Zn supplementation increased (P<0.05) the number of graafian follicles and corpus luteum with no effect on primary, secondary and tertiary follicle number. The study indicated that rats fed organic sources of Zn had higher antioxidant enzyme activities, immune response and serum progesterone concentration with higher number of mature follicles. Though the effect of feeding various organic sources were comparable, rats fed zinc methionine had higher antioxidant activity and cell mediated immune response was higher in rats on Zn propionate.

Keywords: organic zinc, immune, rats, reproductive

Procedia PDF Downloads 286

Authors: Michael Zhang, Nicholas Marriage, Valerie Astle, Marie-Louise Ratican, Jonathan Ash, Haddijatou Hughes

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Objective: Young infants are often brought to the Emergency Department (ED) with a variety of complaints, some of them are non-specific and present as a diagnostic challenge to the attending clinician. Whilst invasive investigations such as blood tests and lumbar puncture are necessary in some cases to exclude serious infections, some basic clinical tools in additional to thorough clinical history can be useful to assess the risks of serious conditions in these young infants. This study aimed to examine the utilization of one of clinical tools in this regard. Methods: This retrospective observational study examined the medical records of infants under 6 months presenting to a mixed urban ED between January 2013 and December 2014. The infants deemed to have non-specific complaints or diagnoses by the emergency clinicians were selected for analysis. The ones with clear systemic diagnoses were excluded. Among all relevant clinical information and investigation results, utilization of Standard Paediatric Observation Chart (SPOC) was particularly scrutinized in these medical records. This specific chart was developed by the expert clinicians in local health department. It categorizes important clinical signs into some color-coded zones as a visual cue for serious implication of some abnormalities. An infant is regarded as SPOC positive when fulfills 1 red zone or 2 yellow zones criteria, and the attending clinician would be prompted to investigate and treat for potential serious conditions accordingly. Results: Eight hundred and thirty-five infants met the inclusion criteria for this project. The ones admitted to the hospital for further management were more likely to have SPOC positive criteria than the discharged infants (Odds ratio: 12.26, 95% CI: 8.04 – 18.69). Similarly, Sepsis alert criteria on SPOC were positive in a higher percentage of patients with serious infections (56.52%) in comparison to those with mild conditions (15.89%) (p < 0.001). The SPOC sepsis criteria had a sensitivity of 56.5% (95% CI: 47.0% - 65.7%) and a moderate specificity of 84.1% (95% CI: 80.8% - 87.0%) to identify serious infections. Applying to this infant population, with a 17.4% prevalence of serious infection, the positive predictive value was only 42.8% (95% CI: 36.9% - 49.0%). However, the negative predictive value was high at 90.2% (95% CI: 88.1% - 91.9%). Conclusions: Standard Paediatric Observation Chart has been applied as a useful clinical tool in the clinical practice to help identify and manage young sick infants in ED effectively.

Keywords: clinical tool, infants, non-specific complaints, Standard Paediatric Observation Chart

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Authors: Fuad Abdullah Alatawi

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Microbial infections-based diseases are a significant public health issue around the world, mainly when antibiotic-resistant bacterium types evolve. In this research, we explored the anti-bacterial and anti-cancer potency of iron-oxide (Fe₂O₃) nanoparticles prepared from F. macrocarpa fruit extract. The chemical composition of F. macrocarpa fruit extract was used as a reducing and capping agent for nanoparticles’ synthesis was examined by GC-MS/MS analysis. Then, the prepared nanoparticles were confirmed by various biophysical techniques, including X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), UV-Vis Spectroscopy, and Transmission Electron Microscopy (TEM) and Energy Dispersive Spectroscopy (EDAX), and Dynamic Light Scattering (DLS). Also, the antioxidant capacity of fruit extract was determined through 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), Fluorescence Recovery After Photobleaching (FRAP), Superoxide Dismutase (SOD) assays. Furthermore, the cytotoxicity activities of Fe₂O₃ NPs were determined using the (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) (MTT) test on MCF-7 cells. In the antibacterial assay, lethal doses of the Fe₂O₃NPs effectively inhibited the growth of gram-negative and gram-positive bacteria. The surface damage, ROS production, and protein leakage are the antibacterial mechanisms of Fe₂O₃NPs. Concerning antioxidant activity, the fruit extracts of F. macrocarpa had strong antioxidant properties, which were confirmed by DPPH, ABTS, FRAP, and SOD assays. In addition, the F. microcarpa-derived iron oxide nanomaterials greatly reduced the cell viability of (MCF-7). The GC-MS/MS analysis revealed the presence of 25 main bioactive compounds in the F. microcarpa extract. Overall, the finding of this research revealed that F. microcarpa-derived Fe₂O₃ nanoparticles could be employed as an alternative therapeutic agent to cure microbial infection and breast cancer in humans.

Keywords: ficus microcarpa, iron oxide, antibacterial activity, cytotoxicity

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Authors: R. Raudonis, L. Raudonė, V. Janulis, P. Viškelis

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Pharmacological and clinical studies demonstrated that phenolic compounds particularly flavonoids and phenolic acids are responsible for a wide spectrum of therapeutic activities. Flavonoids and phenolic acids are regarded as natural antioxidants that play an important role in protecting cells from oxidative stress. Qualitatively prepared dry extracts possess high stability and concentration of bio active compounds, facility of standardization and quality control. The aim of this work was to determine the phenolic and antioxidant profiles of Hippophaë rhamnoides L., Betula pendula Roth., Tilia cordata Mill., Sorbus aucuparia L. leaves dry extracts and to identify markers of antioxidant activity. Extracts were analyzed using high-performance liquid chromatography (HPLC) with FRAP post-column assay. Dry extracts are versatile forms possessing wide area of applications, final product ensure consistent phytochemical and functional properties. Seven flavonoids: rutin, hyperoside, isorhamnetin 3-O-rutinoside, isorhamnetin 3-O-glucoside, quercetin, kaempferol, isorhamnetin were identified in dry extract of Hippophaë rhamnoides L. leaves. Predominant compounds were flavonol glycosides which were chosen as markers for quantitative control of dry extracts. Chlorogenic acid, hyperoside, rutin, quercetin, isorhamnetin were prevailing compounds in Betula pendula Roth. leaves extract, whereas strongest ferric reducing activity was determined for chlorogenic acid and hyperoside. Notable amounts of protocatechuic acid and flavonol glycosides, rutin, hyperoside, quercitrin, isoquercitrin were identified in the chromatographic profile of Tilia cordata Mill. Neochlorogenic and chlorogenic acids were significantly dominant compounds in antioxidant profile in dry extract of Sorbus aucuparia L. leaves. Predominant compounds of antioxidant profiles could be proposed as functional markers of quality of phenolic rich raw materials. Dry extracts could be further used for manufacturing of pharmaceutical and nutraceuticals.

Keywords: dry extract, FRAP, antioxidant activity, phenolic

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Authors: Masoomeh Alsadat Mirshafaei

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The present study aims to explore the effect of an 8-week aerobic training regimen combined with cinnamon extract on serum irisin and leptin levels in insulin-resistant rats. Additionally, this research leverages various machine learning (ML) and deep learning (DL) algorithms to model the complex interdependencies between exercise, nutrition, and metabolic markers, offering a groundbreaking approach to obesity and diabetes research. Forty-eight Wistar rats were selected and randomly divided into four groups: control, training, cinnamon, and training cinnamon. The training protocol was conducted over 8 weeks, with sessions 5 days a week at 75-80% VO2 max. The cinnamon and training-cinnamon groups were injected with 200 ml/kg/day of cinnamon extract. Data analysis included serum data, dietary intake, exercise intensity, and metabolic response variables, with blood samples collected 72 hours after the final training session. The dataset was analyzed using one-way ANOVA (P<0.05) and fed into various ML and DL models, including Support Vector Machines (SVM), Random Forest (RF), and Convolutional Neural Networks (CNN). Traditional statistical methods indicated that aerobic training, with and without cinnamon extract, significantly increased serum irisin and decreased leptin levels. Among the algorithms, the CNN model provided superior performance in identifying specific interactions between cinnamon extract concentration and exercise intensity, optimizing the increase in irisin and the decrease in leptin. The CNN model achieved an accuracy of 92%, outperforming the SVM (85%) and RF (88%) models in predicting the optimal conditions for metabolic marker improvements. The study demonstrated that advanced ML and DL techniques could uncover nuanced relationships and potential cellular responses to exercise and dietary supplements, which is not evident through traditional methods. These findings advocate for the integration of advanced analytical techniques in nutritional science and exercise physiology, paving the way for personalized health interventions in managing obesity and diabetes.

Keywords: aerobic training, cinnamon extract, insulin resistance, irisin, leptin, convolutional neural networks, exercise physiology, support vector machines, random forest

Procedia PDF Downloads 37

Authors: Zohreh Bayat, Dariush Minai-Tehrani

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Pseudomonas aeruginosa is a Gram-negative, rode shape and aerobic bacterium that has shown to be resistance to many antibiotics. This resistance makes the bacterium very harmful in some diseases. It can also generate diseases in any part of the gastrointestinal tract from oropharynx to rectum. P. aeruginosa has become an important cause of infection, especially in patients with compromised host defense mechanisms. One of the most important reasons that make P. aeruginosa an emerging opportunistic pathogen in patients is its ability to use various compounds as carbon sources. Lipase is an enzyme that catalyzes the hydrolysis of lipids. Most lipases act at a specific position on the glycerol backbone of lipid substrate. Some lipases are expressed and secreted by pathogenic organisms during the infection. Muscarinic antagonist used as an antispasmodic and in urinary incontinence. The drug has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. Aim: In this study the inhibitory effect of a muscarinic antagonist on lipase of P. aeruginosa was investigated. Methods: P. aeruginosa was cultured in minimal salt medium with 1% olive oil as carbon source. The cells were harvested and the supernatant, which contained lipase, was used for enzyme assay. Results: Our results showed that the drug can inhibit P. aeruginosa lipase by competitive manner. In the presence of different concentrations of the drug, the Vmax (2 mmol/min/mg protein) of enzyme did not change, while the Km raised by increasing the drug concentration. The Ki (inhibition constant) and IC50 (the half maximal inhibitory concentration) value of drug was estimated to be about 30 uM and 60 uM which determined that the drug binds to enzyme with high affinity. Maximum activity of the enzyme was observed at pH 8 in the absence and presence of muscarinic antagonist, respectively. The maximum activity of lipase was observed at 600C and the enzyme became inactive at 900C. Conclusion: The muscarinic antagonist drug could inhibit lipase of P. aeruginosa and changed the kinetic parameters of the enzyme. The drug binded to enzyme with high affinity and did not chang the optimum pH of the enzyme. Temperature did not affect the binding of drug to musmuscarinic antagonist.

Keywords: Pseudomonas aeruginosa, drug, enzyme, inhibition

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Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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Authors: Donghee Kang

Abstract:

Background: Cancer pain is very difficult to control as the mechanism of pain is varied, and the patient has several co-morbidities. The use of Intravenous Patient-Controlled Analgesia (IV-PCA) can effectively control underlying pain and breakthrough pain. Ketamine is used in many pain patients due to its unique analgesic effect. In this study, it was checked whether there was a difference in the amount of analgesic usage, pain control degree, and side effects between patients who controlled pain with fentanyl-based IV-PCA and those who added Ketamine for pain control. Methods: Among the patients referred to this department for cancer pain, IV-PCA was applied to patients who were taking sufficient oral analgesics but could not control them or had blood clotting disorders that made the procedure difficult, and this patient group was targeted. In IV-PCA, 3000 mcg of Fentanyl, 160 mg of Nefopam, and 0.3 mg of Ramosetrone were mixed with normal saline to make a total volume of 100 ml. Group F used this IV-PCA as it is, and group K mixed 250 mg of Ketamine with normal saline to make a total volume of 100 ml. For IV-PCA, the basal rate was 0.5ml/h, the bolus was set to 1ml when pressed once, and the lockout time was set to 15 minutes. If pain was not controlled after IV-PCA application, 500 mcg of Fentanyl was added, and if excessive sedation or breathing difficulties occurred, the use was stopped for one hour. After that, the degree of daily pain control, analgesic usage, and side effects were investigated for seven days using this IV-PCA. Results: There was no difference between the two groups in the demographic data. Both groups had adequate pain control. Initial morphine milligram equivalents did not differ between the two groups, but the total amount of Fentanyl used for seven days was significantly different between the two groups [p=0.014], and group F used more Fentanyl through IV-PCA. In addition, the amount of sleeping pills used during the seven days was higher in Group F [p<0.01]. Overall, there was no difference in the frequency of side effects between the two groups, but the nausea was more frequent in Group F [p=0.031]. Discussion: When the two groups were compared, pain control was good in both groups. This seems to be because Fentanyl-based IV-PCA showed an adequate pain control effect. However, there was a significant difference in the total amount of opioid (Fentanyl) used, which is thought to be the opioid-sparing effect of Ketamine. Also, among the side effects, nausea was significantly less, which is thought to be possible because the amount of opioids used in the Ketamine group was small. The frequency of requesting sleeping pills was significantly less in the group using Ketamine, and it seems that Ketamine also helped improve sleep quality. In conclusion, using Ketamine with an opioid to control pain seems to have advantages. IV-PCA, which can be used effectively when other procedures are difficult, is more effective and safer when used together with Ketamine than opioids alone.

Keywords: cancer pain, intravenous patient-controlled analgesia, Ketamine, opioid

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Authors: G. St-Pierre-Lemieux, E. Askari Mahvelati, D. Groleau, P. Proulx

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Mathematical modeling has become an important tool for the study of foam behavior. Computational Fluid Dynamic (CFD) can be used to investigate the behavior of foam around foam breakers to better understand the mechanisms leading to the ‘destruction’ of foam. The focus of this investigation was the simple cone foam breaker, whose performance has been identified in numerous studies. While the optimal pumping angle is known from the literature, the contribution of pressure drop, shearing, and centrifugal forces to the foam syneresis are subject to speculation. This work provides a screening of those factors against changes in the cone angle and foam rheology. The CFD simulation was made with the open source OpenFOAM toolkits on a full three-dimensional model discretized using hexahedral cells. The geometry was generated using a python script then meshed with blockMesh. The OpenFOAM Volume Of Fluid (VOF) method was used (interFOAM) to obtain a detailed description of the interfacial forces, and the model k-omega SST was used to calculate the turbulence fields. The cone configuration allows the use of a rotating wall boundary condition. In each case, a pair of immiscible fluids, foam/air or water/air was used. The foam was modeled as a shear thinning (Herschel-Buckley) fluid. The results were compared to our measurements and to results found in the literature, first by computing the pumping rate of the cone, and second by the liquid break-up at the exit of the cone. A 3D printed version of the cones submerged in foam (shaving cream or soap solution) and water, at speeds varying between 400 RPM and 1500 RPM, was also used to validate the modeling results by calculating the torque exerted on the shaft. While most of the literature is focusing on cone behavior using Newtonian fluids, this works explore its behavior in shear thinning fluid which better reflects foam apparent rheology. Those simulations bring new light on the cone behavior within the foam and allow the computation of shearing, pressure, and velocity of the fluid, enabling to better evaluate the efficiency of the cones as foam breakers. This study contributes to clarify the mechanisms behind foam breaker performances, at least in part, using modern CFD techniques.

Keywords: bioreactor, CFD, foam breaker, foam mitigation, OpenFOAM

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Authors: Frida Carrillo Morales, Maria Maricela Carrasco Yépez, Saúl Rojas Hernández

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Naegleria fowleri is the causative agent of primary amebic meningoencephalitis, this disease is acute and fulminant that affects humans. It has been reported that despite the existence of therapeutic options against this disease, its mortality rate is 97%. Therefore, the need arises to have vaccines that confer protection against this disease and, in addition to developing adjuvants to enhance the immune response. In this regard, in our work group, we obtained a peptide designed from the membrane protein MP2CL5 of Naegleria fowleri called Smp145 that was shown to be immunogenic; however, it would be of great importance to enhance its immunological response, being able to co-administer it with a non-toxic adjuvant. Therefore, the objective of this work was to carry out the bioinformatic design of a peptide of the Naegleria fowleri membrane protein MP2CL5 conjugated with a non-toxic modified adjuvant from the native A1 structure of Cholera Toxin. For which different bioinformatics tools were used to obtain a model with a modification in amino acid 61 of the A1 subunit of the CT (CTA1), to which the Smp145 peptide was added and both molecules were joined with a 13-glycine linker. As for the results obtained, the modification in CTA1 bound to the peptide produces a reduction in the toxicity of the molecule in in silico experiments, likewise, the prediction in the binding of Smp145 to the receptor of B cells suggests that the molecule is directed in specifically to the BCR receptor, decreasing its native enzymatic activity. The stereochemical evaluation showed that the generated model has a high number of adequately predicted residues. In the ERRAT test, the confidence with which it is possible to reject regions that exceed the error values was evaluated, in the generated model, a high score was obtained, which determines that the model has a good structural resolution. Therefore, the design of the conjugated peptide in this work will allow us to proceed with its chemical synthesis and subsequently be able to use it in the mouse meningitis protection model caused by N. fowleri.

Keywords: immunology, vaccines, pathogens, infectious disease

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Authors: Cenza Rhoda, Falone Sunda, Elvis Kidzeru, Nonhlanhla P. Khumalo, Afolake Arowolo

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Introduction: The human FAM111B gene mutations are associated with POIKTMP, a rare multi-organ fibrosing disease. Recent studies also reported the overexpression of FAM111B in specific cancers. However, the role of FAM111B in these pathologies, particularly fibrosarcoma, remains unknown. Materials and Methods: FAM111B RNA expression in some cancer cell lines was assessed in silico and validated in vitro in these cell lines and skin fibroblasts derived from the South African family member affected by POIKTMP with the heterozygous FAM111B gene mutation: NM_198947.4: c.1861T>G (p. Tyr621Asp or Y621D) by qPCR and western blot. The cellular function of FAM111B was also studied in HT1080 using various cell-based functional assays and a simple and cost-effective PCR-RFLP method for genotyping/screening FAM111B gene mutations described. Results: Expression studies showed upregulated FAM111B mRNA and protein in the cancer cells. High FAM111B expression with robust nuclear localization occurred in HT1080. Additionally, expression data and cell-based assays indicated that FAM111B led to the upregulation of cell migration and decreased cell apoptosis and cell proliferation modulation. FAM111B Y621D mutation showed similar effects on cell migration but minimal impact on cell apoptosis. FAM111B mRNA and protein expression were markedly downregulated (p ≤ 0.05) in the patient's skin-derived fibroblasts. Lastly, the PCR-RFLP method successfully genotyped FAM111B Y621D gene mutation. Discussion: FAM111B is a cancer-associated nuclear protein: Its modulation by mutations may enhance cell migration and proliferation and decrease apoptosis, as seen in cancers and POIKTMP/fibrosis, thus representing a viable therapeutic target in these disorders. Furthermore, the PCR-RFLP method could prove a valuable tool for FAM111B mutation validation or screening in resource-constrained laboratories.

Keywords: FAM111B, POIKTMP, cancer, fibrosis, PCR-RFLP

Procedia PDF Downloads 121

Authors: Zakaria Baka, Halima Alem

Abstract:

Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.

Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques

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Authors: Ruben L. Tagare, Jr

Abstract:

This study was conducted to determine the parents’ motivating factors for their deaf and mute children to participate in physical and recreational activities. Data were collected from the 17 parents of the deaf and mute children using a specifically designed survey questionnaire as the primary instrument used in the study. Data analysis and interpretation were done with the aid of descriptive statistics, such as frequency, percentage, weighted mean and multiple responses. Most of the respondents were female with a mean average age of 38 years old. The average age of their children was 10 years old. In terms of monthly income, the respondents had an average monthly income of PhP 13,945. Furthermore, most of the respondents lived in the urban area and were all Catholic by faith or religion. As to the factors that parents used to motivate their deaf and mute children to engage in physical and recreational activities, these included the followings: First; to make my child experience and explore more meaningful things through physical and recreational activities; second; to gain other’s respect; third; to build friendship and interact with his peers; fourth; to experience the feeling of belongingness; and fifth: to learn and discover new things. On the other hand, the least chosen factors were: first; to help achieve and maintain a healthy weight; second; to reduce fats and lowering blood pressure; third; to improve balance, coordination and strength; fourth; to improve posture; and fifth; to assist the child in the development of gross motor and fine motor skills. Based on the findings of the study, it is hereby recommended that since the first factor is 'to make my child experience and explore more meaningful things through physical and recreational activities' and the other top factors are more on social aspect, the school should design extra-curricular activities such as theatrical play and other similar activities that the students will find interesting while the parents will be more motivated to engage their children into physical and recreational activities. Also, since the least chosen factors are more on physical aspect, the school should organize or conduct a seminar for the parents to be aware of the benefits of participating in physical and recreational activities for their deaf and mute children. They can also conduct an information campaign to encourage the other parents of deaf and mute children, whom they keep only inside their home to enroll in the school and let their children be exposed to the natural world. Considering that parents are the primary motivators that can best help their children become more interested in physical and recreational activities for their own development, the school should always remain motivated by creating activities for the deaf and mute children with their parents. The study also recommends conducting further study on the level of knowledge/understanding of the parents on the benefits that can be derived from participating in physical and recreational activities.

Keywords: deaf and mute, participation, physical and recreational activities, adaptive PE

Procedia PDF Downloads 182

Authors: Breanna Macumber, Victor A. Huayamave, Emir A. Vela, Wangdo Kim, Tamara T. Chamber, Esteban Centeno

Abstract:

Spina bifida is a type of neural tube defect that affects the nervous system and can lead to problems such as total leg paralysis. Treatment requires physical therapy and rehabilitation. Robotic exoskeletons have been used for rehabilitation to train muscle movement and assist in injury recovery; however, current models focus on the adult populations and not on the infant population. The proposed framework aims to couple a musculoskeletal infant model with a robotic exoskeleton using vacuum-powered artificial muscles to provide rehabilitation to infants affected by spina bifida. The study that drove the input values for the robotic exoskeleton used motion capture technology to collect data from the spontaneous kicking movement of a 2.4-month-old infant lying supine. OpenSim was used to develop the musculoskeletal model, and Inverse kinematics was used to estimate hip joint angles. A total of 4 kicks (A, B, C, D) were selected, and the selection was based on range, transient response, and stable response. Kicks had at least 5° of range of motion with a smooth transient response and a stable period. The robotic exoskeleton used a Vacuum-Powered Artificial Muscle (VPAM) the structure comprised of cells that were clipped in a collapsed state and unclipped when desired to simulate infant’s age. The artificial muscle works with vacuum pressure. When air is removed, the muscle contracts and when air is added, the muscle relaxes. Bench testing was performed using a 6-month-old infant mannequin. The previously developed exoskeleton worked really well with controlled ranges of motion and frequencies, which are typical of rehabilitation protocols for infants suffering with spina bifida. However, the random kicking motion in this study contained high frequency kicks and was not able to accurately replicate all the investigated kicks. Kick 'A' had a greater error when compared to the other kicks. This study has the potential to advance the infant rehabilitation field.

Keywords: musculoskeletal modeling, soft robotics, rehabilitation, pediatrics

Procedia PDF Downloads 118