Search results for: genetic aetiology

Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Anna Solovyeva, Ivan Levakin, Nickolai Galaktionov, Olga Podgornaya

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Animals that reproduce asexually were thought to have the same genotypes within generations for a long time. However, some refuting examples were found, and mobile genetic elements (MGEs) or transposons are considered to be the most probable source of genetic instability. Dispersed nature and the ability to change their genomic localization enables MGEs to be efficient mutators. Hence the study of MGEs genomic impact requires an appropriate object which comprehends both representative amounts of various MGEs and options to evaluate the genomic influence of MGEs. Animals that reproduce asexually seem to be a decent model to study MGEs impact in genomic variability. We found a small marine trematode Himasthla elongata (Himasthlidae) to be a good model for such investigation as it has a small genome size, diverse MGEs and parthenogenetic stages in the lifecycle. In the current work, clonal diversity of cercaria was traced with an AFLP (Amplified fragment length polymorphism) method, diverse zones from electrophoretic patterns were cloned, and the nature of the fragments explored. Polymorphic patterns of individual cercariae AFLP-based fingerprints are enriched with retrotransposons of different families. The bulk of those sequences are represented by open reading frames of non-Long Terminal Repeats containing elements(non-LTR) yet Long-Terminal Repeats containing elements (LTR), to a lesser extent in variable figments of AFLP array. The CR1 elements expose both in polymorphic and conservative patterns are remarkably more frequent than the other non-LTR retrotransposons. This data was confirmed with shotgun sequencing-based on Illumina HiSeq 2500 platform. Individual cercaria of the same clone (i.e., originated from a single miracidium and inhabiting one host) has a various distribution of MGE families detected in sequenced AFLP patterns. The most numerous are CR1 and RTE-Bov retrotransposons, typical for trematode genomes. Also, we identified LTR-retrotransposons of Pao and Gypsy families among DNA transposons of CMC-EnSpm, Tc1/Mariner, MuLE-MuDR and Merlin families. We detected many of them in H. elongata transcriptome. Such uneven MGEs distribution in AFLP sequences’ sets reflects the different patterns of transposons spreading in cercarial genomes as transposons affect the genome in many ways (ectopic recombination, gene structure interruption, epigenetic silencing). It is considered that they play a key role in the origins of trematode clonal polymorphism. The authors greatly appreciate the help received at the Kartesh White Sea Biological Station of the Russian Academy of Sciences Zoological Institute. This work is funded with RSF 19-74-20102 and RFBR 17-04-02161 grants and the research program of the Zoological Institute of the Russian Academy of Sciences (project number AAAA-A19-119020690109-2).

Keywords: AFLP, clonal polymorphism, Himasthla elongata, mobile genetic elements, NGS

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Authors: Yasaman Mohammadi

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Executive functions are a critical component of goal-directed behavior, encompassing a diverse set of cognitive processes such as working memory, cognitive flexibility, and inhibitory control. These functions are known to decline with age, but the precise mechanisms underlying this decline remain unclear. This paper provides an in-depth review of recent research investigating age-related changes in executive functions, drawing on insights from neuroimaging, genetics, and cognitive neuroscience. Through an interdisciplinary approach, this paper offers a nuanced understanding of the complex interplay between neural mechanisms, genetic factors, and cognitive processes that contribute to executive function decline in aging. Here, we investigate how different neuroimaging methods, like functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), have helped scientists better understand the brain bases for age-related declines in executive function. Additionally, we discuss the role of genetic factors in mediating individual differences in executive functions across the lifespan, as well as the potential for cognitive interventions to mitigate age-related decline. Overall, this paper presents a comprehensive and integrative view of the current state of knowledge regarding age-related changes in executive functions. It underscores the need for continued interdisciplinary research to fully understand the complex and dynamic nature of executive function decline in aging, with the ultimate goal of developing effective interventions to promote healthy cognitive aging.

Keywords: executive functions, aging, neuroimaging, cognitive neuroscience, working memory, cognitive training

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Authors: B. Nageshwar Rao

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Urinary tract infection (UTI) represents the most commonly acquired bacterial infection worldwide, with substantial morbidity, mortality, and economic burden. The objective of the study is to characterize the microbial profiles of uropathogenic in the obstetric population by RTPCR. Study design: An observational cross-sectional study was performed at a single tertiary health care hospital among 50 pregnant women with UTIs, including asymptomatic and symptomatic patients attending the outpatient department and inpatient department of Obstetrics and Gynaecology.Methods: Serotyping and genes detection of various uropathogens were studied using RTPCR. Pulse filed gel electrophoresis methods were used to determine the various genetic profiles. Results: The present study shows that CsgD protein, involved in biofilm formation in Escherichia coli, VIM1, IMP1 genes for Klebsiella were identified by using the RTPCR method. Our results showed that the prevalence of VIM1 and IMP1 genes and CsgD protein in E.coli showed a significant relationship between strong biofilm formation, and this may be due to the prevalence of specific genes. Finally, the genetic identification of RTPCR results for both bacteria was correlated with each other and concluded that the above uropathogens were common isolates in producing Biofilm in the pregnant woman suffering from urinary tract infection in our hospital observational study.

Keywords: biofilms, Klebsiella, E.coli, urinary tract infection

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Authors: Zerrin Orbak, Busra Demir

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Osteopetrosis is a rare genetic disease characterized by impaired bone resorption and increased bone sclerosis. Clinical presentation is very different in osteopetrosis. It can be asymptomatic or can be seen with typical symptoms. Here, a case of osteopetrosis was presented when evaluated for nystagmus. She was 10 months old. Parents were second-degree relatives. On physical examination, pigeon chest deformity and horizontal nystagmus were observed. There was a failure of thrive but no fracture. The cardiovascular examination was normal. Cranial, vertebral and long bone roentgenograms revealed characteristic deformities of osteopetrosis and diffuse sclerosis. The diagnosis was confirmed by genetic testing. A Homozygous mutation was detected in the TNFRSF11A gene (c.508A>G p.(Arg170Gly)). RANKL is encoded by the tumor necrosis factor ligand superfamily member 11 (TNFSF11) gene, and the binding to its receptor RANK, encoded by the TNFRSF11A gene, determines the activation of the downstream pathway that drives osteoclast differentiation and activation (51). The complete absence of osteoclasts is the key feature of the osteoclast-poor form of osteopetrosis (46). Patients are characterized by the absence of TRAP-positive osteoclasts in bone biopsies. The osteoclast-poor subtype of osteopetrosis caused by mutations in TNFSF11 gene is ultra-rare in humans. Clinical presentation is usually severe, with onset in early infancy or in fetal life. But here, a case was presented with horizontal nystagmus. A case presented with horizontal nystagmus, which was evaluated by neurology and diagnosed incidentally, was shared.

Keywords: osteopetrosis, nystagmus, bone, osteoclast-poor

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Authors: Eun Jeong Yu, Inn Soo Kang, Tae Ki Yoon, Mi Kyoung Koong

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Advanced female age is associated with higher cycle cancelation rates, lower clinical pregnancy rate, increased miscarriage and aneuploidy rates in IVF (In Vitro Fertilization) cycles. This retrospective cohort study was conducted at a Cha Fertility Center, Seoul Station. All fresh non-donor IVF cycles performed in women aged 40 years and above from January 2016 to December 2016 were reviewed. Donor/recipient treatment, PGD/PGS (Preimplantation Genetic Diagnosis/ Preimplantation Genetic Screening) were excluded from analysis. Of the 1,166 cycles from 753 women who completed ovulation induction, 1,047 were appropriate for the evaluation according to inclusion and exclusion criterion. IVF cycles were categorized according to age and grouped into the following 1-year age groups: 40, 41, 42, 43, 44, 45 and > 46. The mean age of patients was 42.4 ± 1.8 years. The median AMH (Anti-Mullerian Hormone) level was 1.2 ± 1.5 ng/mL. The mean number of retrieved oocytes was 4.9 ± 4.3. The clinical pregnancy rate and live birth rate in women > 40 years significantly decreased with each year of advancing age (p < 0.001). The clinical pregnancy rate decreased from 21% at the age of 40 years to 0% at ages above 45 years. Live birth rate decreased from 12.3% to 0%, respectively. There were no clinical pregnancy outcomes among 95 patients aged above 45 years of age. The overall miscarriage rate was 40.7% (range, 36.7%-70%). The transfer of at least one good quality embryo was associated with about 4-9% increased chance of a clinical pregnancy rate. Therefore, IVF in old age women less than 46 had a reasonable chance for successful pregnancy outcomes especially when good quality embryo is transferred.

Keywords: advanced maternal age, in vitro fertilization, pregnancy rate, live birth rate

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Authors: V. Pizarro-Carmona, S. Castano-Solis, M. Cortés-Carmona, J. Fraile-Ardanuy, D. Jimenez-Bermejo

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The purpose of this article is to optimize the Equivalent Electric Circuit Model (EECM) of different orders to obtain greater precision in the modeling of Li-ion battery packs. Optimization includes considering circuits based on 1RC, 2RC and 3RC networks, with a dependent voltage source and a series resistor. The parameters are obtained experimentally using tests in the time domain and in the frequency domain. Due to the high non-linearity of the behavior of the battery pack, Genetic Algorithm (GA) was used to solve and optimize the parameters of each EECM considered (1RC, 2RC and 3RC). The objective of the estimation is to minimize the mean square error between the measured impedance in the real battery pack and those generated by the simulation of different proposed circuit models. The results have been verified by comparing the Nyquist graphs of the estimation of the complex impedance of the pack. As a result of the optimization, the 2RC and 3RC circuit alternatives are considered as viable to represent the battery behavior. These battery pack models are experimentally validated using a hardware-in-the-loop (HIL) simulation platform that reproduces the well-known New York City cycle (NYCC) and Federal Test Procedure (FTP) driving cycles for electric vehicles. The results show that using GA optimization allows obtaining EECs with 2RC or 3RC networks, with high precision to represent the dynamic behavior of a battery pack in vehicular applications.

Keywords: Li-ion battery packs modeling optimized, EECM, GA, electric vehicle applications

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Authors: Abejide Dorcas Ropo, Falusi Olamide Ahmed, Daudu Oladipupo Abdulazeez Yusuf, Muhammad Liman Muhammad, Gado Aishatu Adamu

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Bambara groundnut is an indigenous African legume with great potential to tackle the problem of food insecurity in Nigeria. A germplasm collection mission was carried out in collaboration with the Agricultural Developments Project (ADP) Extension officers of Nigeria between October and December 2014. Bambara groundnut seeds were collected from farmers in different States in Nigeria, such as Kaduna, Niger, Kogi, Benue, Plateau, Adamawa, Nasarawa, Jigawa, Enugu, and Federal Capital Territoy (FCT) Abuja. Some seeds were also collected from National Centre for Genetic Resources and Biotechnology (NACGRAB). The seeds were phenotyped using the descriptor list of Vigna subterranea produced by the International Plant Genetic Resource Institute. A total of 45 original seed lots were collected, which comprised of mixed seeds having different seed coat colours (15) and pure seeded accessions having the same seed coat and eye colour (30). After sorting, a total of 83 accessions were derived from the 45 original seed lots collected, and a total of 24 distinct seed morphotypes with varying seed coat colours and eye colours were identified from the collections. They include cream ( cream ash eye, cream plain eye, and cream black eye), cream purplish spots, cream brown spots/stripe, cream black stripe, cream dark brown patches, cream light grey spots, cream black patches, black, red, light red, dark red, brownish red, brown speckled with black, red speckled with black, brown, brown with brown pattern below hilum, brown with black pattern below hilum, cream black, grey brown, grey black and variegated red. The highest number of accessions were collected from NACGRAB (11), followed by Niger State (10), and the lowest from Benue, Jigawa, and Adamawa States (2). Niger State also had the highest number of mixed seeds. The different seed phenotypes observed in the study are important for the field production of true-to-type lines and can be exploited for the genetic improvement of the Bambara groundnut.

Keywords: Bambara groundnut, characterization, collection, germplasm, phenotypic

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Authors: Maria Luisa Nozawa Ribeiro, Maria Teresa Miceli Kerbauy

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This paper aims to present the theories of public participation in order to understand the context of the public GMO (Genetic Modified Organisms) policies in Brazil, highlighting the characteristics of its configuration and the dialog with the experts. As a controversy subject, the commercialization of GMO provoked manifestation of some popular and environmental representative groups questioning the decisions of policy makers and experts on the matter. Many aspects and consequences of the plantation and consumption of this crops emerged and the safety of this technology was questioned. Environmentalists, Civil Right's movement, representatives of rural workers, farmers and organics producers, etc. demonstrated their point of view, also sustained by some experts of medical, genetical, environmental, agronomical sciences, etc. fields. Despite this movement, the precautionary principle (risk management), implemented in 1987, suggested precaution facing new technologies and innovations in the sustainable development society. This principle influenced many legislation and regulation on GMO around the world, including Brazil, which became a reference among the world regulatory GMO systems. The Brazilian legislation ensures the citizens participation on GMO discussion, characteristic that was important to establish the connection between the subject and the participation theory. These deliberation spaces materialized in Brazil through the "Public Audiences", which are managed by the National Biosafety Technical Commission (CTNBio), the department responsible for controlling the research, production and commercialization of GMOs in Brazil.

Keywords: public engagement, public participation, science and technology studies, transgenic politics

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Authors: Sibusiso Trevor Tshabalala, Samuel Lubbe, Vince Vuledzani Ndou

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Dependency on chemicals has had many disadvantages in pest management control strategies. Such genetic rodenticide resistance and secondary exposure risk are what is currently being experienced. Emphasis on integrated pest management suggests that to control future pests, early intervention and economic threshold development are key starting points in crop production. The significance of this research project is to help establish a relationship between Giant African Land Snail (Achatina Fulica) solution extract, its shell chemical properties, and farmer’s perceptions of biological control in eThekwini Municipality Agri-hubs. A mixed design approach to collecting data will be explored using a trial layout in the field and through interviews. The experimental area will be explored using a split-plot design that will be replicated and arranged in a randomised complete block design. The split-plot will have 0, 10, 20 and 30 liters of water to one liter of snail solution extract. Plots were 50 m² each with a spacing of 12 m between each plot and a plant spacing of 0.5 m (inter-row) ‘and 0.5 m (intra-row). Trials will be irrigated using sprinkler irrigation, with objective two being added to the mix every 4-5 days. The expected outcome will be improved soil fertility and micro-organisms population proliferation.

Keywords: giant african land snail, integrated pest management, photosynthesis, genetic rodenticide resistance, control future pests, shell chemical properties

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Authors: Anita Singh, Richa Naula, Manoj Raghav

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Nutrient rich and high-yielding varieties of fenugreek can be developed by using genotypes which are naturally high in nutrients. Gene banks harbour scanty germplasm collection of Trigonella spp. and a very little background information about its genetic diversity. The extent of genetic diversity in a specific breeding population depends upon the genotype included in it. The present investigation aims at the estimation of macronutrient (phosphorus by spectrophotometer and potassium by flame photometer), micronutrients, namely, iron, zinc, manganese, and copper from seeds of fenugreek genotypes using atomic absorption spectrophotometer, protein by Rapid N Cube Analyser and Steroidal Saponins. Twenty-eight genotypes of fenugreek along with two standard checks, namely, Pant Ragini and Pusa Early Bunching were collected from different parts of India, and nutrient contents of each genotype were determined at G. B. P. U. A. & T. Laboratory, Pantnagar. Highest potassium content was observed in PFG-35 (1207 mg/100g). PFG-37 and PFG-20 were richest in phosphorus, iron and manganese content among all the genotypes. The lowest zinc content was found in PFG-26 (1.19 mg/100g), while the maximum zinc content was found in PFG- 28 (4.43 mg/100g). The highest content of copper was found in PFG-26 (1.97 mg/100g). PFG-39 has the highest protein content (29.60 %). Significant differences were observed in the steroidal saponin among the genotypes. Saponin content ranged from 0.38 g/100g to 1.31 g/100g. Steroidal Saponins content was found the maximum in PFG-36 (1.31 g/100g) followed by PFG-17 (1.28 g/100g). Therefore, the genotypes which are rich in nutrient and oil content can be used for plant biofortification, dietary supplements, and herbal products.

Keywords: genotypes, macronutrients, micronutrient, protein, seeds

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Authors: Maha Ali Al-Mohaya, Lubna Majed Al-Otaibi, Ebtissam Nassir Al-Bakr, Abdulrahman Al-Asmari

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Objectives: Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines play an important role in the pathogenesis and disease progression of OLP. The purpose of this study was to investigate the association of tumor necrosis factor (TNF)-α, TNF-β and interleukin (IL)-10 gene polymorphisms with the OLP risk. Material and Methods: Forty-two unrelated patients with OLP and 211 healthy volunteers were genotyped for TNF-α (-308 G/A), TNF-β (+252A/G), IL-10 (-1082G/A), IL-10 (-819C/T), and IL-10 (-592C/A) polymorphisms. Results: The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher while allele G and GG genotypes were lower in OLP patients as compared to the controls (P < 0.001). The frequency of GA genotype of TNF-β (+252A/G) was significantly higher in patients than in controls while the AA genotype was completely absent in OLP patients. These results indicated that allele A and genotype GA of TNF-α (-308G/A) as well as the GA genotype of TNF-β (+252A/G) polymorphisms are associated with OLP risk. The frequencies of alleles and genotypes of -1082G/A, -819C/T and -592C/A polymorphisms in IL-10 gene did not differ significantly between OLP patients and controls (P > 0.05). However, haplotype ATA extracted from 1082G/A, -819C/T, -592C/A polymorphisms of IL-10 were more prevalent in OLP patients when compared to controls indicating its possible association with OLP susceptibility. Conclusion: It is concluded that TNF-α (-308G/A), TNF-β (+252A/G) and IL-10 (-1082G/A, -819C/T and -592C/A) polymorphisms are associated with the susceptibility of OLP, thus giving additional support for the genetic basis of this disease. Further studies are required using a larger sample size to confirm this association and determine the prognostic values of these findings.

Keywords: oral lichen planus, cytokines, polymorphism, genetic

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Authors: Mohammed N. Al Kindi, Mazin Al Khabouri, Khalsa Al Lamki, Tommasso Pappuci, Giovani Romeo, Nadia Al Wardy

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Hereditary hearing loss is a heterogeneous group of complex disorders with an overall incidence of one in every five hundred newborns presented as syndromic and non-syndromic forms. Cadherin-related 23 (CDH23) is one of the listed deafness causative genes. CDH23 is found to be expressed in the stereocilia of hair cells and the retina photoreceptor cells. Defective CDH23 has been associated mostly with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic (USH1D) or non-syndromic SNHL (DFNB12). An Omani family diagnosed clinically with severe-profound sensorineural hearing loss was genetically analysed by whole exome sequencing technique. A novel homozygous missense variant, c.A7451C (p.D2484A), in exon 53 of CDH23 was detected. One hundred and thirty control samples were analysed where all were negative for the detected variant. The variant was analysed in silico for pathogenicity verification using several mutation prediction software. The variant proved to be a pathogenic mutation and is reported for the first time in Oman and worldwide. It is concluded that in silico mutation prediction analysis might be used as a useful molecular diagnostics tool benefiting both genetic counseling and mutation verification. The aspartic acid 2484 alanine missense substitution might be the main disease-causing mutation that damages CDH23 function and could be used as a genetic hearing loss marker for this particular Omani family.

Keywords: Cdh23, d2484a, in silico, Oman

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Authors: Nafiseh Noormohammadi, Ahmad Sobhani Najafabadi

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Hypericins (hypericin and pseudohypericin) are natural napthodianthrone derivatives produced by Hypericum perforatum (St. John’s Wort), which have many medicinal properties such as antitumor, antineoplastic, antiviral, and antidepressant activities. Production and accumulation of hypericin in the plant are influenced by both genetic and environmental conditions. Despite the existence of different high-throughput data on the plant, genetic dimensions of hypericin biosynthesis have not yet been completely understood. In this research, 21 high-quality RNA-seq data on different parts of the plant were integrated into metabolic data to reconstruct a coexpression network. Results showed that a cluster of 30 transcripts was correlated with total hypericin. The identified transcripts were divided into three main groups based on their functions, including hypericin biosynthesis genes, transporters, detoxification genes, and transcription factors (TFs). In the biosynthetic group, different isoforms of polyketide synthase (PKSs) and phenolic oxidative coupling proteins (POCPs) were identified. Phylogenetic analysis of protein sequences integrated into gene expression analysis showed that some of the POCPs seem to be very important in the biosynthetic pathway of hypericin. In the TFs group, six TFs were correlated with total hypericin. qPCR analysis of these six TFs confirmed that three of them were highly correlated. The identified genes in this research are a rich resource for further studies on the molecular breeding of H. perforatum in order to obtain varieties with high hypericin production.

Keywords: hypericin, St. John’s Wort, data mining, transcription factors, secondary metabolites

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Authors: Ming-Jong Yao, Chin-Sum Shui, Chih-Han Wang

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This paper is developed based on a real-world decision scenario that an industrial gas company that applies the Vendor Managed Inventory model and supplies liquid oxygen with a self-operated heterogeneous vehicle fleet to hospitals in nearby cities. We name it as a Joint Replenishment and Heterogeneous Vehicle Routing Problem with Cyclical Schedule and formulate it as a non-linear mixed-integer linear programming problem which simultaneously determines the length of the planning cycle (PC), the length of the replenishment cycle and the dates of replenishment for each customer and the vehicle routes of each day within PC, such that the average daily operation cost within PC, including inventory holding cost, setup cost, transportation cost, and overtime labor cost, is minimized. A solution method based on genetic algorithm, embedded with an encoding and decoding mechanism and local search operators, is then proposed, and the hash function is adopted to avoid repetitive fitness evaluation for identical solutions. Numerical experiments demonstrate that the proposed solution method can effectively solve the problem under different lengths of PC and number of customers. The method is also shown to be effective in determining whether the company should expand the storage capacity of a customer whose demand increases. Sensitivity analysis of the vehicle fleet composition shows that deploying a mixed fleet can reduce the daily operating cost.

Keywords: cyclic inventory routing problem, joint replenishment, heterogeneous vehicle, genetic algorithm

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Authors: Murali Munisamy, Gauthaman Karunakaran, Mubarak Al-Gahtany, Vivekanandhan Subbiah, M. Manjari Tripati

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Background: Sodium valproate is a widely prescribed broad-spectrum anti-epileptic drug. It shows high inter-individual variability in pharmacokinetics and pharmacodynamics and has a narrow therapeutic range. We evaluated the effects of polymorphic uridine diphosphate glucuronosyltransferase (UGT1A9) metabolizing enzyme on the pharmacokinetics of sodium valproate in the patients with epilepsy who showed toxicity to therapy. Methods: Genotype analysis of the patients was made with polymerase chain–restriction fragment length polymorphism (RFLP) with sequencing. Plasma drug concentrations were measured with reversed phase high-performance liquid chromatography (HPLC) and concentration–time data were analyzed by using a non-compartmental approach. Results: The results of this study suggested a significant genotypic as well as allelic association with valproic acid toxicity for UGT1A9 polymorphic enzymes. The elimination half-life (t 1/2=40.2 h) of valproic acid was longer and the clearance rate (CL=937 ml/h) was lower in the poor metabolizers group of UGT1A9 polymorphism who showed toxicity than in the intermediate metabolizers group (t1/2=35.5 h, CL=1042 ml/h) or the extensive metabolizers group (t1/2=26. h, CL=1,302 ml/h). Conclusion: Our findings suggest that the UGT1A9 genetic polymorphism plays a significant role in the steady state concentration of sodium valproate, and it thereby has an impact on the toxicity of the sodium valproate used in the patients with epilepsy.

Keywords: UGT1A9, sodium valporate, pharmacogenetics, polymorphism

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Authors: Minhas Alam, Muhammad Hidayat Rasool, Mohsin Khurshid, Bilal Aslam

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Acinetobacter baumannii is a notorious bacterial pathogen that is an emerging nightmare in clinical settings and is mainly involved in severe nosocomial infections. However, the data related to carbapenem-resistant A. baumannii (CRAB) from veterinary settings is limited, especially in developing countries like Pakistan. To investigate the genetic diversity and molecular basis of carbapenem resistance in Acinetobacter baumannii isolates from Cattle, a total of 1960 samples were collected from cattle from Punjab, Pakistan. The isolates were analyzed by routine microbiological procedures and confirmed by polymerase chain reaction (PCR). The isolates were further screened for antimicrobial susceptibility and the presence of multiple antimicrobial-resistant determinants by PCR. Multilocus sequence typing (MLST) was performed. The results of the current study revealed that the overall prevalence of A. baumannii in cattle was 3.28% (65/1980). Among cattle 27.7% (18/65) were found CRAB strains. The CRAB isolates harbor class D β- lactamases genes, e-g, blaOXA-23 and blaOXA-51, 94.4% (17/18). CRAB isolates carry class B β- lactamases gene blaIMP, and only one isolate carries the blaNDM-1 gene. The MLST results of CRAB isolates from cattle demonstrated 5 STs and one new ST. The commonly found sequence types in CRAB isolates were ST2 (n=10, 55.5%), followed by ST642 (n=5, 27.8%) and ST600 & ST889 (n=1, 5.55%). The presence of CRAB isolates in cattle indicates an alarming situation in Punjab, Pakistan. Immediate control measures should be taken to stop the transmission of CRAB isolates within cattle, to the environment, and to clinical settings.

Keywords: acinetobacter baumannii, carbapenemases, veterinary, drug resistance

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Authors: Ha T. T. Ly, Truc B. Truc, Hai N. Truong, Mai P. T. Nguyen, Ngoc D. Ngo, Khanh V. Tran, Hai T. Le

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Beta thalassemia is one of the most common inherited blood disorders, which is characterized by decreased or absent in beta globin expression. Patients with Beta thalassemia whose anemia is not so severe as to necessitate transfusions are said to have thalassemia intermedia. Objective: The goal of this study is prenatal diagnosis for pregnancy woman with Beta thalassemia intermedia and her husband with Beta thalassemia carrier at high risk of Beta thalassemia major in Northern of Vietnam. Material and method: The family has a 6 years-old compound heterozygous thalassemia major for CD71/72(+A) and Hbb:c. -78A>G/nt-28(A>G) male child. The father was heterozygous for CD71/72(+A) mutation which is Beta plus type and the mother was compound heterozygosity of two different variants, namely, Hbb: c. -78A>G/nt-28(A>G) and CD26(A-G) HbE. Prenatal Beta thalassemia mutation detection in fetal DNA was carried out using multiplex Amplification-refractory mutation system ARMS-PCR and confirmed by direct Sanger-sequencing Hbb gene. Prenatal diagnoses were perfomed by amniotic fluid sampling from pregnant woman in the 16-18th week of pregnancy after the genotypes of parents of the probands were identified. Result: When amniotic fluid sample was analyzed for Beta globin gene (Hbb), we found that the genotype is heterozygous for CD71/72(+A) and CD26(A-G) HbE. This genotype is different from the 1st child of this family. Conclusion: Prenatal diagnosis helps the parents to know the genotype and the thalassemia status of the fetus, so they can have early decision on their pregnancy. Genetic diagnosis provided a useful method in diagnosis for familial members in pedigree, genetic counseling and prenatal diagnosis.

Keywords: beta thalassemia intermedia, Hbb gene, pedigree, prenatal diagnosis

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Authors: Boukhalfa Djemouai, Belkadi Souhila, Safsaf Boubakeur

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To increase the profitability of the national herd so that it can meet the needs of the population, Algeria has proceeded to the introduction of new reproductive biotechnologies, including artificial insemination on natural heat, by induction and heat synchronization. This biotechnology uses the male way for the creation and dissemination of genetic progress. The study has focused on 30 goat kids and bucks local breed aged between 03 and 24 months, divided into 03 groups 03-06 months[Grp 1; n=9], 07-10 months [Grp 2; n=13] and 11-24 months [Grp 3; n=8], in order to determine the influence of age on testicular evolution by measurements of testis and scrotum, and the epididymis sperm parameters evaluation. These parameters are influenced by age variations (sperm and spermocytogram). The examined parameters have focused on testicular weight (grams), the scrotal circumference (cm), mass mobility (%), vitality rate (%), sperm concentration (x 109), and percentage of abnormal spermatozoa (%). The ANOVA reveals a significance effect of age on parameters: testis weight, scrotal circumference, sperm concentration, motility varying between high (p < 0.01) to very high significance (p < 0.001), while in viability and abnormalities no significance was observed between all groups. The value of these parameters increased significantly until the age of 02 years, while that of sperm abnormalities has increased in Grp2. The histological study of testicular development shows that the genetic spermatozoa function characterized by cell proliferation, which is more and more intense starting from the age of 05 months and can be considered as an age of puberty in the local breed goat Arbia and increases with animal age.

Keywords: kids and bucks, epididymis sperm, testicular measurements, Arbia breed

Procedia PDF Downloads 117

Authors: A. Gopala Krishna, M. Lakshmi Chaitanya, V. Kalyana Manohar

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In the existent analysis, laser micro machining (LMM) of Silicon carbide (SiCp) reinforced Aluminum 7075 Metal Matrix Composite (Al7075/SiCp MMC) was studied. While machining, Because of the intense heat generated, A layer gets formed on the work piece surface which is called recast layer and this layer is detrimental to the surface quality of the component. The recast layer needs to be as small as possible for precise applications. Therefore, The height of recast layer and the depth of groove which are conflicting in nature were considered as the significant manufacturing criteria, Which determines the pursuit of a machining process obtained in LMM of Al7075/10%SiCp composite. The present work formulates the depth of groove and height of recast layer in relation to the machining parameters using the Response Surface Methodology (RSM) and correspondingly, The formulated mathematical models were put to use for optimization. Since the effect of machining parameters on the depth of groove and height of recast layer was contradictory, The problem was explicated as a multi objective optimization problem. Moreover, An evolutionary Non-dominated sorting genetic algorithm (NSGA-II) was employed to optimize the model established by RSM. Subsequently this algorithm was also adapted to achieve the Pareto optimal set of solutions that provide a detailed illustration for making the optimal solutions. Eventually experiments were conducted to affirm the results obtained from RSM and NSGA-II.

Keywords: Laser Micro Machining (LMM), depth of groove, Height of recast layer, Response Surface Methodology (RSM), non-dominated sorting genetic algorithm

Procedia PDF Downloads 337

Authors: Dibakar Chakrabarty, Mebada Suiting

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Rapid urbanization coupled with changes in land use pattern results in increasing peak discharge and shortening of catchment time of concentration. The consequence is floods, which often inundate roads and inhabited areas of cities and towns. Management of storm water resulting from rainfall has, therefore, become an important issue for the municipal bodies. Proper management of storm water obviously includes adequate design of storm water drainage networks. The design of storm water network is a costly exercise. Least cost design of storm water networks assumes significance, particularly when the fund available is limited. Optimal design of a storm water system is a difficult task as it involves the design of various components, like, open or closed conduits, storage units, pumps etc. In this paper, a methodology for least cost design of storm water drainage systems is proposed. The methodology proposed in this study consists of coupling a storm water simulator with an optimization method. The simulator used in this study is EPA’s storm water management model (SWMM), which is linked with Genetic Algorithm (GA) optimization method. The model proposed here is a mixed integer nonlinear optimization formulation, which takes care of minimizing the sectional areas of the open conduits of storm water networks, while satisfactorily conveying the runoff resulting from rainfall to the network outlet. Performance evaluations of the developed model show that the proposed method can be used for cost effective design of open conduit based storm water networks.

Keywords: genetic algorithm (GA), optimal design, simulation-optimization, storm water network, SWMM

Procedia PDF Downloads 232

Authors: Ruzanna Muradyan

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Medical data mining is a crucial field in contemporary healthcare that offers cutting-edge tactics with enormous potential to transform patient care. This abstract examines how sophisticated data mining techniques could transform the healthcare industry, with a special focus on how they might improve patient outcomes. Healthcare data repositories have dynamically evolved, producing a rich tapestry of different, multi-dimensional information that includes genetic profiles, lifestyle markers, electronic health records, and more. By utilizing data mining techniques inside this vast library, a variety of prospects for precision medicine, predictive analytics, and insight production become visible. Predictive modeling for illness prediction, risk stratification, and therapy efficacy evaluations are important points of focus. Healthcare providers may use this abundance of data to tailor treatment plans, identify high-risk patient populations, and forecast disease trajectories by applying machine learning algorithms and predictive analytics. Better patient outcomes, more efficient use of resources, and early treatments are made possible by this proactive strategy. Furthermore, data mining techniques act as catalysts to reveal complex relationships between apparently unrelated data pieces, providing enhanced insights into the cause of disease, genetic susceptibilities, and environmental factors. Healthcare practitioners can get practical insights that guide disease prevention, customized patient counseling, and focused therapies by analyzing these associations. The abstract explores the problems and ethical issues that come with using data mining techniques in the healthcare industry. In order to properly use these approaches, it is essential to find a balance between data privacy, security issues, and the interpretability of complex models. Finally, this abstract demonstrates the revolutionary power of modern data mining methodologies in transforming the healthcare sector. Healthcare practitioners and researchers can uncover unique insights, enhance clinical decision-making, and ultimately elevate patient care to unprecedented levels of precision and efficacy by employing cutting-edge methodologies.

Keywords: data mining, healthcare, patient care, predictive analytics, precision medicine, electronic health records, machine learning, predictive modeling, disease prognosis, risk stratification, treatment efficacy, genetic profiles, precision health

Procedia PDF Downloads 43

Authors: Saria Almarzook, Monika Reissmann, Gudrun Brockmann

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Due to its history, occurrence in different ecosystems and diverse using, the modern horse (Equus caballus) shows large variability in size, appearance, behavior and habits. At all times, breeders try to create groups (breeds, strains) representing high homology but showing clear differences in comparison to other groups. A great interest of analyzing phenotypic and genetic traits looking for real diversity and genetic uniqueness existents for Arabian horses in Syria. 90 Arabian horses from governmental research center of Arabian horses in Damascus were included. The horses represent three strains (Kahlawi, Saklawi, Hamdani) originated from different geographical zones. They were raised on the same farm, under stable conditions. Twelve phenotypic traits were measured: wither height (WH), croup width (CW), croup height (CH), neck girth (NG), thorax girth (TG), chest girth (ChG), chest depth (ChD), chest width (ChW), back line length (BLL), body length (BL), fore cannon length (FCL) and hind cannon length (HCL). The horses were divided into groups according to age (less than 2 years, 2-4 years, 4-9 years, over 9 years) and to sex (male, female). The statistical analyzes show that age has significant influence of WH while the strain has only a very limited effect. On CW, NG, BLL, FCL and HCL, there is only a significant influence of sex. Age has significant effect on CH and BL. All sources of classes have a significant effect on TG, ChG, ChD and ChW. Strain has a significant effect on the BL. These results provide first information for real biodiversity in and between the strains and can be used to develop the breeding work in the Arabian horse breed.

Keywords: Arabian horse, phenotypic traits, strains, Syria

Procedia PDF Downloads 381

Authors: Nadia Belu, Laurenţiu Mihai Ionescu, Agnieszka Misztal

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The automotive industry is one of the most important industries in the world that concerns not only the economy, but also the world culture. In the present financial and economic context, this field faces new challenges posed by the current crisis, companies must maintain product quality, deliver on time and at a competitive price in order to achieve customer satisfaction. Two of the most recommended techniques of quality management by specific standards of the automotive industry, in the product development, are Failure Mode and Effects Analysis (FMEA) and Control Plan. FMEA is a methodology for risk management and quality improvement aimed at identifying potential causes of failure of products and processes, their quantification by risk assessment, ranking of the problems identified according to their importance, to the determination and implementation of corrective actions related. The companies use Control Plans realized using the results from FMEA to evaluate a process or product for strengths and weaknesses and to prevent problems before they occur. The Control Plans represent written descriptions of the systems used to control and minimize product and process variation. In addition Control Plans specify the process monitoring and control methods (for example Special Controls) used to control Special Characteristics. In this paper we propose a computer-aided solution with Genetic Algorithms in order to reduce the drafting of reports: FMEA analysis and Control Plan required in the manufacture of the product launch and improved knowledge development teams for future projects. The solution allows to the design team to introduce data entry required to FMEA. The actual analysis is performed using Genetic Algorithms to find optimum between RPN risk factor and cost of production. A feature of Genetic Algorithms is that they are used as a means of finding solutions for multi criteria optimization problems. In our case, along with three specific FMEA risk factors is considered and reduce production cost. Analysis tool will generate final reports for all FMEA processes. The data obtained in FMEA reports are automatically integrated with other entered parameters in Control Plan. Implementation of the solution is in the form of an application running in an intranet on two servers: one containing analysis and plan generation engine and the other containing the database where the initial parameters and results are stored. The results can then be used as starting solutions in the synthesis of other projects. The solution was applied to welding processes, laser cutting and bending to manufacture chassis for buses. Advantages of the solution are efficient elaboration of documents in the current project by automatically generating reports FMEA and Control Plan using multiple criteria optimization of production and build a solid knowledge base for future projects. The solution which we propose is a cheap alternative to other solutions on the market using Open Source tools in implementation.

Keywords: automotive industry, FMEA, control plan, automotive technology

Procedia PDF Downloads 397

Authors: Ante Turudic, Filip Varga, Zlatko Liber, Jernej Jakse, Zlatko Satovic, Ivan Radosavljevic, Martina Grdisa

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Microsatellites (SSRs) are highly informative repetitive sequences of 2-6 base pairs, which are the most used molecular markers in assessing the genetic diversity of plant species. Dalmatian pyrethrum (Tanacetum cinerariifolium /Trevir./ Sch. Bip) is an outcrossing diploid (2n = 18) endemic to the eastern Adriatic coast and source of the natural insecticide pyrethrin. Due to the high repetitiveness and large size of the genome (haploid genome size of 9,58 pg), previous attempts to develop microsatellite markers using the standard methods were unsuccessful. A next-generation sequencing (NGS) approach was applied on genomic DNA extracted from fresh leaves of Dalmatian pyrethrum. The sequencing was conducted using NovaSeq6000 Illumina sequencer, after which almost 400 million high-quality paired-end reads were obtained, with a read length of 150 base pairs. Short reads were assembled by combining two approaches; (1) de-novo assembly and (2) joining of overlapped pair-end reads. In total, 6.909.675 contigs were obtained, with the contig average length of 249 base pairs. Of the resulting contigs, 31.380 contained one or multiple microsatellite sequences, in total 35.556 microsatellite loci were identified. Out of detected microsatellites, dinucleotide repeats were the most frequent, accounting for more than half of all microsatellites identifies (21,212; 59.7%), followed by trinucleotide repeats (9,204; 25.9%). Tetra-, penta- and hexanucleotides had similar frequency of 1,822 (5.1%), 1,472 (4.1%), and 1,846 (5.2%), respectively. Contigs containing microsatellites were further filtered by SSR pattern type, transposon occurrences, assembly characteristics, GC content, and the number of occurrences against the draft genome of T. cinerariifolium published previously. After the selection process, 50 microsatellite loci were used for primer design. Designed primers were tested on samples from five distinct populations, and 25 of them showed a high degree of polymorphism. The selected loci were then genotyped on 20 samples belonging to one population resulting in 17 microsatellite markers. Availability of codominant SSR markers will significantly improve the knowledge on population genetic diversity and structure as well as complex genetics and biochemistry of this species. Acknowledgment: This work has been fully supported by the Croatian Science Foundation under the project ‘Genetic background of Dalmatian pyrethrum (Tanacetum cinerariifolium /Trevir/ Sch. Bip.) insecticidal potential’ - (PyrDiv) (IP-06-2016-9034).

Keywords: genome assembly, NGS, SSR, Tanacetum cinerariifolium

Procedia PDF Downloads 118

Authors: Vaibhav Barve

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Reversible information hiding has drawn a lot of interest as of late. Being reversible, we can restore unique computerized data totally. It is a plan where mystery data is put away in digital media like image, video, audio to maintain a strategic distance from unapproved access and security reason. By and large JPEG bit stream is utilized to store this key data, first JPEG bit stream is encrypted into all around sorted out structure and then this secret information or key data is implanted into this encrypted region by marginally changing the JPEG bit stream. Valuable pixels suitable for information implanting are computed and as indicated by this key subtle elements are implanted. In our proposed framework we are utilizing RC4 algorithm for encrypting JPEG bit stream. Encryption key is acknowledged by framework user which, likewise, will be used at the time of decryption. We are executing enhanced least significant bit supplanting steganography by utilizing genetic algorithm. At first, the quantity of bits that must be installed in a guaranteed coefficient is versatile. By utilizing proper parameters, we can get high capacity while ensuring high security. We are utilizing logistic map for shuffling of bits and utilization GA (Genetic Algorithm) to find right parameters for the logistic map. Information embedding key is utilized at the time of information embedding. By utilizing precise picture encryption and information embedding key, the beneficiary can, without much of a stretch, concentrate the incorporated secure data and totally recoup the first picture and also the original secret information. At the point when the embedding key is truant, the first picture can be recouped pretty nearly with sufficient quality without getting the embedding key of interest.

Keywords: data embedding, decryption, encryption, reversible data hiding, steganography

Procedia PDF Downloads 279

Authors: Seungchul Lee, Minjeong Kim, Iman Janghorban Esfahani, Jeong Tai Kim, ChangKyoo Yoo

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It is hard to maintain the effluent quality of the wastewater treatment plants (WWTPs) under with fixed types of operational control because of continuously changed influent flow rate and pollutant load. The aims of this study is development of multi-loop multi-objective control (ML-MOC) strategy in plant-wide scope targeting four objectives: 1) maximization of nutrient removal efficiency, 2) minimization of operational cost, 3) maximization of CH4 production in anaerobic digestion (AD) for CH4 reuse as a heat source and energy source, and 4) minimization of N2O gas emission to cope with global warming. First, benchmark simulation mode is modified to describe N2O dynamic in biological process, namely benchmark simulation model for greenhouse gases (BSM2G). Then, three types of single-loop proportional-integral (PI) controllers for DO controller, NO3 controller, and CH4 controller are implemented. Their optimal set-points of the controllers are found by using multi-objective genetic algorithm (MOGA). Finally, multi loop-MOC in BSM2G is implemented and evaluated in BSM2G. Compared with the reference case, the ML-MOC with the optimal set-points showed best control performances than references with improved performances of 34%, 5% and 79% of effluent quality, CH4 productivity, and N2O emission respectively, with the decrease of 65% in operational cost.

Keywords: Benchmark simulation model for greenhouse gas, multi-loop multi-objective controller, multi-objective genetic algorithm, wastewater treatment plant

Procedia PDF Downloads 491

Authors: Micheale Yifter Weldemichael, Hailay Mehari Gebremedhn, Teklehaimanot Hailesslasie Teklu

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Recent developments in targeted genome editing accelerated genetic research and opened new potentials to improve crops for better yields and quality. Given the significance of cereal crops as a primary source of food for the global population, the utilization of contemporary genome editing techniques like CRISPR/Cas9 is timely and crucial. CRISPR/Cas technology has enabled targeted genomic modifications, revolutionizing genetic research and exploration. Application of gene editing through CRISPR/Cas9 in enhancing sorghum is particularly vital given the current ecological, environmental, and agricultural challenges exacerbated by climate change. As sorghum is one of the main staple foods of our region and is known to be a resilient crop with a high potential to overcome the above challenges, the application of genome editing technology will enhance the investigation of gene functionality. CRISPR/Cas9 enables the improvement of desirable sorghum traits, including nutritional value, yield, resistance to pests and diseases, and tolerance to various abiotic stresses. Furthermore, CRISPR/Cas9 has the potential to perform intricate editing and reshape the existing elite sorghum varieties, and introduce new genetic variations. However, current research primarily focuses on improving the efficacy of the CRISPR/Cas9 system in successfully editing endogenous sorghum genes, making it a feasible and successful undertaking in sorghum improvement. Recent advancements and developments in CRISPR/Cas9 techniques have further empowered researchers to modify additional genes in sorghum with greater efficiency. Successful application and advancement of CRISPR techniques in sorghum will aid not only in gene discovery and the creation of novel traits that regulate gene expression and functional genomics but also in facilitating site-specific integration events. The purpose of this review is, therefore, to elucidate the current advances in sorghum genome editing and highlight its potential in addressing food security issues. It also assesses the efficiency of CRISPR-mediated improvement and its long-term effects on crop improvement and host resistance against parasites, including tissue-specific activity and the ability to induce resistance. This review ends by emphasizing the challenges and opportunities of CRISPR technology in combating parasitic plants and proposing directions for future research to safeguard global agricultural productivity.

Keywords: CRISPR/Cas9, genome editing, quality, sorghum, stress, yield

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Authors: Surekha Rathod

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Sickle cell disease is a vascular disorder characterized by chronic, ongoing organ damage that is punctuated by episodes of acutely painful vascular complications.1 It is the most common genetic blood disorder in the United States, with about 2000 infants being identified through routine blood screenings annually, and an estimated 104,000-138,000 affected individuals living in the United States. Approximately 0.3%-1.3% of African American are affected by Sickle Cell Diseases (SCD).3 The aim of this paper is to present oral health status of patients with SCD. A total of 200 subjects of both sexes in the age group 18- 40 years were included in this study. The subjects were examined and the following indices were recorded • Oral hygiene index – Simplified (OHI-S). • Probing depths (PD). • Clinical Attachment Levels (CAL). • Gingival Index - Loe and Sillness. • Turesky Gillmore Glickman Modification of the Quigley Hein Plaque Index. (1970) • DMFT index. • Sickle Cell Disease Severity Index. A total of 1478 patients were screened of which 200 subjects were found to be diagnosed with SCD by electrophoresis. The study thus, included 200 subjects (111 females & 89 males) diagnosed with Sickle Cell Disease in the age group of 18-40 years. The probing pocket depths (PPD) were measured in millimeters. 36% had PPD in the range of 2-4mm, 48% had PPD in the range of 4-6mm while 16% had PPD of more than 6mm. Similar results were obtained for the Clinical Attachment Levels (CAL). 29.5 % subjects had CAL 2-4mm, 44.5% had 4-6mm & 26% had CAL 6mm & above. We can thus conclude that although oral health is not a priority for patients with SCD, it is supported by increased plaque accumulation. Because of the chronic anemic state of the patients with SCD, they should be encouraged to pay strict attention to oral hygiene instructions and practice.

Keywords: chronic, genetic, oral, sickle cell disease, vascular

Procedia PDF Downloads 390

Authors: Nicholas Bayfield, Liam Bibo, Kaushelandra Rathore, Lucas Sanders, Mark Newman

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INTRODUCTION: Surgical pulmonary embolectomy is an established therapy for acute pulmonary embolism causing right heart dysfunction and haemodynamic instability. Massive intraoperative airway haemorrhage is a rare complication of pulmonary embolectomy. We present our institutional experience with massive airway haemorrhage complicating pulmonary embolectomy and discuss optimal therapeutic strategies. METHODS: A retrospective review of emergent surgical pulmonary embolectomy patients was undertaken. Cases complicated by massive intra-operative airway haemorrhage were identified. Intra- and peri-operative management strategies were analysed and discussed. RESULTS: Of 76 patients undergoing emergent or salvage pulmonary embolectomy, three cases (3.9%) of massive intraoperative airway haemorrhage were identified. Haemorrhage always began on weaning from cardiopulmonary bypass. Successful management strategies involved intraoperative isolation of the side of bleeding, occluding the affected airway with an endobronchial blocker, institution of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) and reversal of anticoagulation. Running the ECMO without heparinisation allows coagulation to occur. Airway haemorrhage was controlled within 24 hours of operation in all patients, allowing re-institution of dual lung ventilation and decannulation from ECMO. One case in which positive end-expiratory airway pressure was trialled initially was complicated by air embolism. Although airway haemorrhage was controlled successfully in all cases, all patients died in-hospital for reasons unrelated to the airway haemorrhage. CONCLUSION: Massive intraoperative airway haemorrhage during pulmonary embolectomy is a rare complication with potentially catastrophic outcomes. Re-perfusion alveolar and capillary injury is the likely aetiology. With a systematic approach to management, airway haemorrhage can be well controlled intra-operatively and often resolves within 24 hours. Stopping blood flow to the pulmonary arteries and support of oxygenation by the institution of VA ECMO is important. This management has been successful in our 3 cases.

Keywords: pulmonary embolectomy, cardiopulmonary bypass, cardiac surgery, pulmonary embolism

Procedia PDF Downloads 168