Search results for: acute phase proteins

Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

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The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

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Authors: Byung Keun Yang, Jae Eun Ku, Young Seon Joo, Je Sung You, Sung Phil Chung, Hahn Shick Lee

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The purpose of this study is to review the evidence comparing the efficacy and safety between L-carnitine and extracorporeal elimination therapy in the management of acute valproic acid L-carnitine vs Extracorporeal Elimination for Acute Valproic acid Intoxication. PubMed, Embase, Cochrane library, Web of Science, KoreaMed, KMbase, and KISS were searched, using the terms carnitine and valproic acid. All studies, regardless of design, reporting efficacy or safety endpoints were included. Reference citations from identified publications were reviewed. Both English and Korean languages were included. Two authors extracted primary data elements including poisoning severity, presenting features, clinical management, and outcomes. Thirty two articles including 33 cases were identified. Poisoning severity was classified as 3 mild, 11 moderate, and 19 severe cases. Nine cases were treated with L-carnitine while 24 cases received extracorporeal therapy without L-carnitine. All patients except one expired patient treated with hemodialysis recovered clinically and no adverse effects were noted. A case report comparing two patients who ingested the same amount of valproic acid showed increased ICU stay (3 vs. 11 days) in case of delayed extracorporeal therapy. Published evidence comparing L-carnitine with extracorporeal therapy is limited. Based on the available evidence, it is reasonable to consider L-carnitine for patients with acute valproic acid overdose. In case of severe poisoning, extracorporeal therapy would also be considered in the early phase of treatment.

Keywords: carnitine, overdose, poisoning, renal dialysis, valproic acid

Procedia PDF Downloads 342

Authors: Yun-Tsuen Chen, Shih-Ting Huang, Pi-Fen Cheng, Yu-Ting Su, Joffrey Hsu, Hui-Zhu Chen

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Acute intestinal obstruction is one of the differentials of acute abdomen and requires timely alleviation of intestinal distention and abdominal pain to avoid perforation, intra-abdominal infection, and peritonitis. Investigation to identify the cause of obstruction will direct treatment planning and allow for more effective management. In this study, we present a 71-year-old female presenting with symptoms of acute intestinal obstruction for five days. After extensive history taking, physical exam, medical imaging, and pathology, the patient was diagnosed with colon cancer with lung metastasis and acute intestinal obstruction. The patient was placed on nil per os status with intravenous fluid support, intravenous antibiotics, and a decompression nasogastric tube was placed. The patient received decompression with colostomy creation surgery. After assessing the patient’s clinical condition and tumor staging, a multidisciplinary healthcare team created an individualized treatment plan, which included plans to prepare the patient for home self-care and maintain good mental health with regular monitoring in the clinic setting. This case demonstrates the importance of early diagnosis, effective treatment, and a multidisciplinary approach to the management of acute intestinal obstruction secondary to colon cancer.

Keywords: acute intestinal obstruction, colostomy surgery, metastatic colon cancer, multidisciplinary healthcare team

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Authors: Abdorrasoul Malekpour, Mohammad Ghorbani Mojtaba Mortazavi, Mohammadreza Fattahi, Mohammad Hassan Meshkibaf, Ali Fakhrzad, Saeid Salehi, Saeideh Zahedi, Amir Ahmadimoghaddam, Parviz Farzadnia Dr., Mohammadreza Hajyani Asl Bs

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Hepatitis B as an infectious disease has eight main genotypes (A–H). The aim of this study is to Bioinformatically identify Rare Codon Clusters (RCC) in proteins structure of HBV. For detection of protein family accession numbers (Pfam) of HBV proteins; used of uni-prot database and Pfam search tool were used. Obtained Pfam IDs were analyzed in Sherlocc program and RCCs in HBV proteins were detected. In further, the structures of TrEMBL entries proteins studied in PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software. Pfam search tool have found nine significant hits and 0 insignificant hits in 3 frames. Results of Pfams studied in the Sherlocc program show this program not identified RCCs in the external core antigen (PF08290) and truncated HBeAg protein (PF08290). By contrast the RCCs become identified in Hepatitis core antigen (PF00906) Large envelope protein S (PF00695), X protein (PF00739), DNA polymerase (viral) N-terminal domain (PF00242) and Protein P (Pf00336). In HBV genome, seven RCC identified that found in hepatitis core antigen, large envelope protein S and DNA polymerase proteins and proteins structures of TrEMBL entries sequences that reported in Sherlocc program outputs are not complete. Based on situation of RCC in structure of HBV proteins, it suggested those RCCs are important in HBV life cycle. We hoped that this study provide a new and deep perspective in protein research and drug design for treatment of HBV.

Keywords: rare codon clusters, hepatitis B virus, bioinformatic study, infectious disease

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Authors: Bouchiha Hanene, Rouabhi Rachid, Bouchama Khaled, Djebar Berrebbah Houraya, Djebar Mohamed Reda

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Recently, some natural products such as essentials oils (EOs) have been used in the fields as alternative to synthetic compounds, to minimize the negative impacts to the environment. This fact has led to questions about the possible impact of EOs on ecosystems. Currently in toxicology, the use of alternative models can help to understand the mechanisms of toxic action, at different levels of organization of ecosystems. Algae, protozoa and bacteria form the base of the food chain and protozoan cells are used as bioindicators often of pollution in environment. Unicellular organisms offer the possibility of direct study of independent cells with specific characteristics of individual cells and whole organisms at the same time. This unicellular facilitates the study of physiological processes, and effects of pollutants at the cellular level, which makes it widely used to assess the toxic effects of various xenobiotics. This study aimed to verify the effects of EOs of one famous plant used tremendously in our folk medicine, namely Artemisia herba alba in causing acute toxicity (24 hours) and chronic (15 days) toxicity for model cellular (Paramecium sp). To this end, cellular’s of paramecium were exposed to various concentrations (Three doses were chosen) of EOs extracted from plant (Artemisia herba alba). In the first experiment, the cellular s cultures were exposed for 48 hours to different concentrations to determine the median lethal concentration (DL50). We followed the evolution of physiological parameters (growth), biochemical (total proteins, respiratory metabolism), as well as the variations of a bio marker the GSH. Our results highlighted a light inhibition of the growth of the protozoa as well as a disturbance of the contents of total proteins and a reduction in the reduced rate of glutathione. The polarographic study revealed a stimulation of the consumption of O2 and this at the treated cells.

Keywords: essential oils, protozoa, bio indicators, toxicity, Growth, bio marker, proteins, polarographic

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Authors: Ahmed A. A. Fadol, Guangji Tong, Wlaa Mohamed

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This paper provides a comprehensive analysis of food insecurity in Sudan, focusing on consumption patterns and their implications, employing the Integrated Food Security Phase Classification (IPC) assessment framework. Years of conflict and economic instability have driven large segments of the population in Sudan into crisis levels of acute food insecurity according to the (IPC). A substantial number of people are estimated to currently face emergency conditions, with an additional sizeable portion categorized under less severe but still extreme hunger levels. In this study, we explore the multifaceted nature of food insecurity in Sudan, considering its historical, political, economic, and social dimensions. An analysis of consumption patterns and trends was conducted, taking into account cultural influences, dietary shifts, and demographic changes. Furthermore, we employ logistic regression and random forest analysis to identify significant independent variables influencing food security status in Sudan. Random forest clearly outperforms logistic regression in terms of area under curve (AUC), accuracy, precision and recall. Forward projections of the IPC for Sudan estimate that 15 million individuals are anticipated to face Crisis level (IPC Phase 3) or worse acute food insecurity conditions between October 2023 and February 2024. Of this, 60% are concentrated in Greater Darfur, Greater Kordofan, and Khartoum State, with Greater Darfur alone representing 29% of this total. These findings emphasize the urgent need for both short-term humanitarian aid and long-term strategies to address Sudan's deepening food insecurity crisis.

Keywords: food insecurity, consumption patterns, logistic regression, random forest analysis

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Authors: Marjan Javanmard

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The rheological properties of dairy products critically depend on the underlying organisation of proteins at multiple length scales. When heated and acidified, milk proteins form particle gel that is viscoelastic, solvent rich, ‘soft’ material. In this work recent developments on the rheology of soft particles suspensions were used to interpret and potentially define the properties of dairy gel structures. It is discovered that at volume fractions below random close packing (RCP), the Maron-Pierce-Quemada (MPQ) model accurately predicts the viscosity of the dairy gel suspensions without fitting parameters; the MPQ model has been shown previously to provide reasonable predictions of the viscosity of hard sphere suspensions from the volume fraction, solvent viscosity and RCP. This surprising finding demonstrates that up to RCP, the dairy gel system behaves as a hard sphere suspension and that the structural aggregates behave as discrete particulates akin to what is observed for microgel suspensions. At effective phase volumes well above RCP, the system is a soft solid. In this region, it is discovered that the storage modulus of the sheared AMG scales with the storage modulus of the set gel. The storage modulus in this regime is reasonably well described as a function of effective phase volume by the Evans and Lips model. Findings of this work has potential to aid in rational design and control of dairy food structure-properties.

Keywords: dairy suspensions, rheology-structure, Maron-Pierce-Quemada Model, Evans and Lips Model

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Authors: Edna Ariste, Richard Standy Coqmar

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Background: Acute respiratory infections are a major public health problem in the world, mainly in vulnerable populations such as newborns, children under five years of age, and the elderly. The objective of this study was to Characterize the cases of acute respiratory infections in infants and under 15 years old hospitalized at the Immaculée Conception Hospital in Cayes from January 1, 2019, to December 31, 2021. Methods: A retrospective descriptive study was conducted on the epidemiology profile of acute respiratory infections hospitalized in the pediatric ward at Immaculée Conception Hospital in Les Cayes from January 2019 to December 2021. The study population consisted of all newborns, infants, and children under 15 years of age diagnosed with respiratory infections at the pediatric service. Data were collected from the hospitalization registers and patient records of this unit. A database was created and used for data collection. Excel and Epi info 7.2 were used for data analysis. Results: A total of 588 cases were identified during the 2019-2021 year. 43.5% (256) were female, and 56.5% (332) were male. The average age was 4, 3. The most affected age group was 1-4 years. The male/female sex ratio was 1.2. The most frequent respiratory infections were respectively pneumonia 44.9%, bronchitis 16.5%, and respiratory distress 10.5%. The mortality rate recorded during this period was 4.4%. Conclusion: Acute respiratory infections are more frequent in young children. It is, therefore, necessary to practice hand hygiene. Reinforce the surveillance of severe acute respiratory infections.

Keywords: acute respiratory infections, pediatrics, cayes, haiti

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Authors: Olivier de Backer, Alexis Khelfi, Olivier Svensek, Axelle Nolmans, Dominique Desnoeck

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The SMC5-SMC6 complex helps replication and repair of DNA double-strand breaks. Nse1, Nse3 and Nse4 are non-SMC components of the complex in which Nse3 stimulates the E3 ubiquitin ligase activity of Nse1 and is required for recruiting the complex on DNA. In most eukaryotes, Nse3 is a single protein, but in eutherians (placental mammals), it belongs to a large family of proteins called MAGE (Melanoma antigen) that share a conserved domain of about 200 aa known as MHD (Mage homology domain). MAGE assembles specific RING and HECT ubiquitin ligases and determines new substrates for ubiquitination. The MHD is required for the interaction with the cognate E3 ligase. Some MAGEs (referred to as Type I) are exclusively expressed in germ cells of the testis but are often expressed ectopically in cancer cells as the result of epigenetic modifications. The 12 MAGE-A genes belong to this category. Serval MAGE-A proteins could promote tumorigenesis by targeting tumor suppressor proteins (including p53) for ubiquitination and degradation. We showed that depletion of MAGE-A proteins in melanoma cells results in impaired DNA damage response and increased double-strand breaks after exposure to camptothecin. Moreover, it was shown that other actors of the DNA Damage Response were impacted when cells were depleted of MAGEA proteins.

Keywords: DNA damage response, melanoma, camptothecin, new role, MAGEA

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Authors: Soniya Nityanand, Ekta Minocha, Manali Jain, Rohit Anthony Sinha, Chandra Prakash Chaturvedi

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Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: amniotic fluid stem cells, acute renal failure, autophagy, cisplatin

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Authors: J. J. Lee, S. R. Sung, E. J. Yum, S. C. Kim, B. H. Hyun, M. Her, H. S. Lee

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Canine brucellosis is a critical problem in dogs leading to reproductive diseases which are mainly caused by Brucella canis. There are, nonetheless, not clear symptoms so that it may go unnoticed in most of the cases. Serodiagnosis for canine brucellosis has not been confirmed. Moreover, it has substantial difficulties due to broad cross-reactivity between the rough cell wall antigens of B. canis and heterospecific antibodies present in normal, uninfected dogs. Thus, this study was conducted to characterize the immunogenic proteins in cytoplasmic antigen (CPAg) of B. canis, which defined the antigenic sensitivity of the humoral antibody responses to B. canis-infected dogs. In analysis of B. canis CPAg, first, we extracted and purified the cytoplasmic proteins from cultured B. canis by hot-saline inactivation, ultrafiltration, sonication, and ultracentrifugation step by step according to the sonicated antigen extract method. For characterization of this antigen, we checked the sort and range of each protein on SDS-PAGE and verified the immunogenic proteins leading to reaction with antisera of B. canis-infected dogs. Selected immunodominant proteins were identified using MALDI-MS/MS. As a result, in an immunoproteomic assay, several polypeptides in CPAg on one or two-dimensional electrophoresis (DE) were specifically reacted to antisera from B. canis-infected dogs but not from non-infected dogs. The polypeptides with approximate 150, 80, 60, 52, 33, 26, 17, 15, 13, 11 kDa on 1-DE were dominantly recognized by antisera from B. canis-infected dogs. In the immunoblot profiles on 2-DE, ten immunodominant proteins in CPAg were detected with antisera of infected dogs between pI 3.5-6.5 at approximate 35 to 10 KDa, without any nonspecific reaction with sera in non-infected dogs. Ten immunodominant proteins identified by MALDI-MS/MS were identified as superoxide dismutase, bacteroferritin, amino acid ABC transporter substrate-binding protein, extracellular solute-binding protein family3, transaldolase, 26kDa periplasmic immunogenic protein, Rhizopine-binding protein, enoyl-CoA hydratase, arginase and type1 glyceraldehyde-3-phosphate dehydrogenase. Most of these proteins were determined by their cytoplasmic or periplasmic localization with metabolism and transporter functions. Consequently, this study discovered and identified the prominent immunogenic proteins in B. canis CPAg, highlighting that those antigenic proteins may accomplish a specific serodiagnosis for canine brucellosis. Furthermore, we will evaluate those immunodominant proteins for applying to the advanced diagnostic methods with high specificity and accuracy.

Keywords: Brucella canis, Canine brucellosis, cytoplasmic antigen, immunogenic proteins

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Authors: Natalie Cutler, Lorna Moxham, Moira Stephens

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Safety is a priority in mental health services, and no more so than in the acute inpatient setting. Mental health service policies and accreditation frameworks commonly approach safety from a risk reduction or elimination perspective leading to service approaches that are arguably more focused on risk than on safety. An exploration what safety means for people who have experienced admission to an acute mental health inpatient unit is currently under way in Sydney, Australia. Using a phenomenographic research approach, this study is seeking to understand the meaning of safety from the perspective of people who use, rather than those who deliver mental health services. Preliminary findings suggest that the meanings of safety for users of mental health services vary from the meanings inherent in the policies and frameworks that inform how mental health services and mental health practice are delivered. This variance has implications for the physical and environmental design of acute mental health inpatient facilities, the policies and practices, and the education and training of mental health staff in particular nurses, who comprise the majority of the mental health workforce. These variances will be presented, along with their implications for the way quality and safety in mental health services are evaluated.

Keywords: acute inpatient, mental health, nursing, phenomenography, recovery, safety

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Authors: Naureen Akhtar

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The stability of the protein in detergent-containing solution is the key for its successful crystallisation. Fluorescence-detection size-exclusion chromatography (FSEC) is a potential approach for screening monodispersity as well as the stability of protein in a detergent-containing-solution. In this present study, covalently linked Green Fluorescent Protein (GFP) to bacterial nitrate transporter, NarU from Escherichia coli was studied for pre-crystallisation trials by FSEC. Immobilised metal ion affinity chromatography (IMAC) and gel filtration were employed for their purification. The main objectives of this study were over-expression, detergent screening and crystallisation of nitrate transporter proteins. This study could not produce enough proteins that could realistically be taken forward to achieve the objectives set for this particular research. In future work, different combinations of variables like vectors, tags, creation of mutant proteins, host cells, position of GFP (N- or C-terminal) and/or membrane proteins would be tried to determine the best combination as the principle of technique is still promising.

Keywords: transporters, detergents, over-expression, crystallography

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Authors: Jiang Xu, Daoping Wang, Yinghong Pan

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The jointing-booting stage is a critical period of both vegetative growth and reproductive growth in rice. Therefore, the proteomic analysis of the mutant Osbri1, whose corresponding gene OsBRI1 encodes the putative BRs receptor OsBRI1, at jointing-booting stage is very important for understanding the effects of BRs on vegetative and reproductive growth. In this study, the proteomes of leaves from an allelic mutant of the DWARF 61 (D61, OsBRI1) gene, Fn189 (dwarf54, d54) and its wild-type variety T65 (Taichung 65) at jointing-booting stage were analysed by using a Q Exactive plus orbitrap mass spectrometer, and more than 3,100 proteins were identified in each sample. Ontology analysis showed that these proteins distribute in various space of the cells, such as the chloroplast, mitochondrion, and nucleus, they functioned as structural components and/or catalytic enzymes and involved in many physiological processes. Moreover, quantitative analysis displayed that 266 proteins were differentially expressed in two samples, among them, 77 proteins decreased and 189 increased more than two times in Fn189 compared with T65, the proteins whose content decreased in Fn189 including b5-like Heme/Steroid binding domain containing protein, putative retrotransposon protein, putative glutaminyl-tRNA synthetase, and higher content proteins such as mTERF, putative Oligopeptidase homologue, zinc knuckle protein, and so on. A former study founded that the transcription level of a mTERF was up-regulated in the leaves of maize seedling after EBR treatment. In our experiments, it was interesting that one mTERF protein increased, but another mTERF decreased in leaves of Fn189 at jointing-booting stage, which suggested that BRs may have differential regulation mechanisms on the expression of various mTERF proteins. The relationship between other differential proteins with BRs is still unclear, and the effects of BRs on rice protein contents and its regulation mechanisms still need further research.

Keywords: bri1 mutant, jointing-booting stage, proteomic analysis, rice

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Authors: Muhammad Mukhtar

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The aim of this study is to evaluate the antioxidant activity and acute toxicity of the extracts of Ficus iteophylla by reactions with 1, 1-diphenyl-2-picryhydrazyl radical (DPPH) and method developed by Lork 1983, respectively. Stem bark of Ficus iteophylla was collected, air dried, pulverized to fine powdered and sequentially extracted using acetone, methanol and water in order of increasing polarity. The result shows strong radical scavenging activity against DPPH for all the extracts when compared with ascorbic acid. The LD50 of 316 mg/kg was calculated for all the three extras, and the values were found to be within the practically toxic range, and therefore, care should be taken when using the plants in traditional medicine.

Keywords: antioxidant, acute toxicity, Ficus iteophylla

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Authors: Hung-Chieh Chen, Kuo-Hui Wang, Tsu-Lin Yeh

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Proteomics represent the performance of genomic complement proteins and the protein level on functional genomics. This study adopted proteomic strategies for comparing serum proteins among three groups: elite sprinter (sprint runner group, SR), long-distance runners (long-distance runner group, LDR), and the untrained control group (control group, CON). Purposes: This study aims to identify elite sprinters and long-distance runners’ serum protein and to provide a comparison of their serum proteome’ composition. Methods: Serum protein fractionations that separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by a quantitative nano-LC-MS/MS-based proteomic profiling. The one-way analysis of variance (ANOVA) and Scheffe post hoc comparison (α= 0.05) was used to determine whether there is any significant difference in each protein level among the three groups. Results: (1) After analyzing the 307 identified proteins, there were 26 unique proteins in the SR group, and 18 unique proteins in the LDR group. (2) For the LDR group, 7 coagulation function-associated proteins’ expression levels were investigated: vitronectin, serum paraoxonase/arylesterase 1, fibulin-1, complement C3, vitamin K-dependent protein, inter-alpha-trypsin inhibitor heavy chain H3 and von Willebrand factor, and the findings show the seven coagulation function-associated proteins were significantly lower than the group of SR. (3) Comparing to the group of SR, this study found that the LDR group’s expression levels of the 2 antioxidant proteins (afamin and glutathione peroxidase 3) were also significantly lower. (4) The LDR group’s expression levels of seven immune function-related proteins (Ig gamma-3 chain C region, Ig lambda-like polypeptide 5, clusterin, complement C1s subcomponent, complement factor B, complement C4-A, complement C1q subcomponent subunit A) were also significantly lower than the group of SR. Conclusion: This study identified the potential serum protein markers for elite sprinters and long-distance runners. The changes in the regulation of coagulation, antioxidant, or immune function-specific proteins may also provide further clinical applications for these two different track athletes.

Keywords: biomarkers, coagulation, immune response, oxidative stress

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Authors: Vineeta Kaushik, Manisha Goel

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Chaperones are proteins that help other proteins fold correctly, and are found in all domains of life i.e., prokaryotes, eukaryotes and archaea. Various comparative genomic studies have suggested that the archaeal protein folding machinery appears to be highly similar to that found in eukaryotes. In case of protein folding; slow rotation of peptide prolyl-imide bond is often the rate limiting step. Formation of the prolyl-imide bond during the folding of a protein requires the assistance of other proteins, termed as peptide prolyl cis-trans isomerases (PPIases). Cyclophilins constitute the class of peptide prolyl isomerases with a wide range of biological function like protein folding, signaling and chaperoning. Most of the cyclophilins exhibit PPIase enzymatic activity and play active role in substrate protein folding which classifies them as a category of molecular chaperones. Till date, there is not very much data available in the literature on archaeal cyclophilins. We aim to compare the structural and biochemical features of the cyclophilin protein from within the three domains to elucidate the features affecting their stability and enzyme activity. In the present study, we carry out in-silico analysis of the cyclophilin proteins to predict their conserved residues, sites under positive selection and compare these proteins to their bacterial and eukaryotic counterparts to predict functional divergence. We also aim to clone and express these proteins in heterologous system and study their biophysical characteristics in detail using techniques like CD and fluorescence spectroscopy. Overall we aim to understand the features contributing to the folding, stability and dynamics of the archaeal cyclophilin proteins.

Keywords: biophysical characterization, x-ray crystallography, chaperone-like activity, cyclophilin, PPIase activity

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Authors: Christina Williams, Mehari Weldemariam, Ann M. Farese, Thomas J. MacVittie, Maureen A. Kane

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Radiation exposure results in dose-dependent and time-dependent multi-organ damage. Drug development of medical countermeasures (MCM) for radiation-induced injury occurs under the FDA Animal Rule because human efficacy studies are not ethical or feasible. The FDA Animal Rule requires the representation of both sexes and describes several uses for biomarkers in MCM drug development studies. Currently, MCMs are limited and there is no FDA-approved biomarker for any radiation injury. Sex as a variable is essential to identifying biomarkers and developing effective MCMs for acute radiation exposure (ARS) and delayed effects of acute radiation exposure (DEARE). These studies aim to address the death of information on sex differences that have not been determined by studies that included only male, single-sex cohorts. Studies have reported differences in radiosensitivity according to sex. As such, biomarker discovery for radiation-induced damage must consider sex as a variable. This study evaluated the plasma proteomic profile of Rhesus macaque non-human primates after different exposures and doses, as well as time points after radiation. Exposures and doses included total body irradiation between 5-7.5 Gy and partial body irradiation with 5% bone marrow sparing at 9, 9.5 and 10 Gy. Timepoints after irradiation included days 1, 3, 60, and 180, which encompassed both acute radiation syndromes and delayed effects of acute radiation exposure. Bottom-up proteomic analyses of plasma included equal numbers of males and females. In the control animals, few proteomic differences are observed between the sexes. In the irradiated animals, there are a few sex differences, with changes mostly consisting of proteins upregulated in the female animals. Multiple canonical pathways were upregulated in irradiated animals relative to the control animals when subjected to pathway analysis, but differential responses between the sexes are limited. These data provide critical baseline differences according to sex and establish sex differences in non-human primate models relevant to drug development of MCM under the FDA Animal Rule.

Keywords: ionizing radiation, sex differences, plasma proteomics, biomarker discovery

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Authors: Akash Bera, Suraj Singh, Jacinta Dsouza, Ramakrishna V. Hosur, Pushpa Mishra

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Ultraviolet C (UVC) radiation induces apoptosis in mammalian cells and it is suggested that the mechanism by which this occurs is the mitochondrial pathway of apoptosis through the release of cytochrome c from the mitochondria into the cytosol. The Bcl-2 family of proteins pro-and anti-apoptotic is the regulators of the mitochondrial pathway of apoptosis. Upon UVC irradiation, the proliferation of apoptosis is enhanced through the downregulation of the anti-apoptotic protein Bcl-xl and up-regulation of Bax. Although the participation of the Bcl-2 family of proteins in apoptosis appears responsive to UVC radiation, to the author's best knowledge, it is unknown how the structure and, effectively, the function of these proteins are directly impacted by UVC exposure. In this background, we present here a structural rationale for the effect of UVC irradiation in restoring apoptosis using two of the relevant proteins, namely, Bid-FL and Bcl-xl ΔC, whose solution structures have been reported previously. Using a variety of biophysical tools such as circular dichroism, fluorescence and NMR spectroscopy, we show that following UVC irradiation, the structures of Bcl-xlΔC and Bid-FL are irreversibly altered. Bcl-xLΔC is found to be more sensitive to UV exposure than Bid-FL. From the NMR data, dramatic structural perturbations (α-helix to β-sheet) are seen to occur in the BH3 binding region, a crucial segment of Bcl-xlΔC which impacts the efficacy of its interactions with pro-apoptotic tBid. These results explain the regulation of apoptosis by UVC irradiation. Our results on irradiation dosage dependence of the structural changes have therapeutic potential for the treatment of cancer.

Keywords: Bid, Bcl-xl, UVC, apoptosis

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Authors: Jafar Ahmadi, Nafiseh Noormohammadi, Sedegeh Fabriki Ourang

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GRF, Growth regulating factor, genes encode a novel class of plant-specific transcription factors. The GRF proteins play a role in the regulation of cell numbers in young and growing tissues and may act as transcription activations in growth and development of plants. Identification of GRF genes and their expression are important in plants to performance of the growth and development of various organs. In this study, to better understanding the structural and functional differences of GRFs family, 45 GRF proteins sequences in A. thaliana, Z. mays, O. sativa, B. napus, B. rapa, H. vulgare, and S. bicolor, have been collected and analyzed through bioinformatics data mining. As a result, in secondary structure of GRFs, the number of alpha helices was more than beta sheets and in all of them QLQ domains were completely in the biggest alpha helix. In all GRFs, QLQ, and WRC domains were completely protected except in AtGRF9. These proteins have no trans-membrane domain and due to have nuclear localization signals act in nuclear and they are component of unstable proteins in the test tube.

Keywords: domain, gene family, GRF, motif

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Authors: Nafisa Komilova, Plamena Angelova, Andrey Abramov, Ulugbek Mirkhodjaev

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder which is induced by the loss of dopaminergic neurons in the midbrain. The mechanism of neurodegeneration is associated with the aggregation of misfolded proteins, oxidative stress, and mitochondrial disfunction. Considering this, the process of removal of unwanted organelles or proteins by autophagy is vitally important in neurons, and activation of these processes could be protective in PD. Short-time acidification of cytosol can activate mitophagy and autophagy, and here we used sodium pyruvate and sodium lactate in human fibroblasts with PD mutations (Pink1, Pink1/Park2, α-syn triplication, A53T) to induce changes in intracellular pH. We have found that both lactate and pyruvate in millimolar concentrations can induce short-time acidification of cytosol in these cells. It induced activation of mitophagy and autophagy in control and PD fibroblasts and protected against cell death. Importantly, the application of lactate to acute brain slices of control and Pink1 knockout mice also induced a reduction of pH in neurons and astrocytes that increase the level of mitophagy. Thus, acidification of cytosol by compounds which play important role in cell metabolism also can activate mitophagy and autophagy and protect cells in the familial form of PD.

Keywords: Parkinson's disease, mutations, mitophagy, autophagy

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Authors: Roni Rachel Mendelson, Caileigh Pudela

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Bacillus cereus is a toxin-producing, facultatively anaerobic gram-positive bacterium that is widely distributed environmentally. It can quickly multiply at room temperature with an abundantly present preformed toxin. When ingested, this toxin can cause gastrointestinal illness, which is the commonly known manifestation of the disease. Bacillus cereus sepsis is a disease that is mostly concerning in the population of the immunocompromised patients. One of them is acute lymphoblastic leukemia’s patients during induction. Pediatric acute lymphoblastic leukemia is a common pediatric hematologic malignancy. It is characterized by the rapid proliferation of poorly differentiated lymphoid progenitor cells inside the bone marrow. We present here a 21-month-old boy undergoing induction chemotherapy for acute lymphoblastic leukemia who developed bacillus sepsis bacteremia and, as a result, multi organ failure leading to seizures and multiple strokes. Our case report highlights the extensive overall and neurological damage that can be caused because of bacillus cereus bacteremia, which can lead to higher mortality rate and decreased in survivorship in a highly curable disease. It is very subtle and difficult to recognize and appears to be deteriorating extremely fast. There should be a low threshold for work up and empiric coverage for neutropenic patients during acute lymphoblastic leukemia induction therapy.

Keywords: acute lymphoblastic leukemia, bacillus cereus, immunocompromised, sepsis

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Authors: Rita Bagheri, Javed Ahmed, Humayra Bashir, M. Irfan Qureshi

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Agriculture lands suffer from a combination of stresses such as salinity and metal contamination including cadmium at the same time. Under such condition of multiple stresses, plant may exhibit unique responses different from the stress occurring individually. Thus, it would be interesting to investigate that how plant respond to combined stress at level of antioxidants and proteome expression, and identifying the proteins which are involved in imparting stress tolerance. With an approach of comparative proteomics and antioxidant analysis, present study investigates the response of Spinacia oleracea to salt (NaCl), cadmium (Cd), and their combination (NaCl+Cd) stress. Two-dimensional gel electrophoresis was used for resolving leaf proteome, and proteins of interest were identified using PDQuest software. A number of proteins expressed differentially, those indicated towards their roles in imparting stress tolerance, were digested by trypsin and analyzed on mass spectrometer for peptide mass fingerprinting (PMF). Data signals were then matched with protein databases using MASCOT. Results show that NaCl, Cd and both together (NaCl+Cd) induce oxidative stress which was highest in combined stress of Cd+NaCl. Correspondingly, the activities of enzymatic antioxidants viz., SOD, APX, GR and CAT, and non-enzymatic antioxidants had highest changes under combined stress compares to single stress over their respective controls. Among the identified proteins, several interesting proteins were identified that may be have role in Spinacia oleracia tolerance in individual and combinatorial stress of salt and cadmium. The functional classification of identified proteins indicates the importance and necessity of keeping higher ratio of defence and disease responsive proteins.

Keywords: Spinacia oleracea, Cd, salinity, proteomics, antioxidants, combinatorial stress

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Authors: Gadiri Sabiha

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Introduction : IgE-dependent cow's milk protein allergy (APLV) is one of the most common allergies in children and is one of the three most common allergies observed in children under 6 years of age. Its natural evolution is most often towards healing. The objective is to determine the sensitization profile of patients allergic to cow's milk (VL). Material and method :A retrospective study carried out on a pediatric population (age < 12 years) over a period of four years (2018-2021) in the context of a suspected food allergy to cow's milk proteins carried out on 121 children aged between 8 months -12 years The search for specific IgE was carried out by immunodot (EUROLINE Pediatric; EUROIMMUN) test which allows a semi-quantitative determination of specific IgE. Results 36 patients (29.7%) had a cow's milk protein allergy (ALPV) with a slight female predominance (58.33% girls vs 41.66% boys) The main clinical signs were: acute diarrhoea; vomiting; Intense abdominal pain, and cutaneous signs (pruritus/urticaria) with respective frequencies of 72%; 58%; 44% and 19%. The 3 major and specific VL allergens identified were beta-lactoglobulin 59% caseins 51% and alpha-lactalbumin 29.7%, The profile of sensitization to LV varies according to age, in infants before 1 year of anti-casein, IgE are predominant 83.3%, followed by beta-lactoglobulin 66.66% and alpha-lactolbumin 50% Conclusion CMPA is a frequent pathology which ranks among the three most common food allergies in children. This is the first to appear, most often starting in infants under 6 months old.

Keywords: specific Ige, food allergy, cow 's milk, child

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Authors: Katerina H. Takova, Ivan N. Minkov, Gergana G. Zahmanova

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Molecular farming is the production of recombinant proteins in plants with the aim to use the protein as a purified product, crude extract or directly in the planta. Plants gain more attention as expression systems compared to other ones due to the cost effective production of pharmaceutically important proteins, appropriate post-translational modifications, assembly of complex proteins, absence of human pathogens to name a few. In addition, transient expression in plant leaves enables production of recombinant proteins within few weeks. Hepatitis E virus (HEV) is a causative agent of acute hepatitis. HEV causes epidemics in developing countries and is primarily transmitted through the fecal-oral route. Presently, all efforts for development of Hepatitis E vaccine are focused on the Open Read Frame 2 (ORF2) capsid protein as it contains epitopes that can induce neutralizing antibodies. For our purpose, we used the CMPV-based vector-pEAQ-HT for transient expression of HEV ORF2 in Nicotiana benthamina. Different molecular analysis (Western blot and ELISA) showed that HEV ORF2 capsid protein was expressed in plant tissue in high-yield up to 1g/kg of fresh leaf tissue. Electron microscopy showed that the capsid protein spontaneously assembled in low abundance virus-like particles (VLPs), which are highly immunogenic structures and suitable for vaccine development. The expressed protein was recognized by both human and swine HEV positive sera and can be used as a diagnostic reagent for the detection of HEV infection. Production of HEV capsid protein in plants is a promising technology for further HEV vaccine investigations. Here, we reported for a rapid high-yield transient expression of a recombinant protein in plants suitable for vaccine production as well as a diagnostic reagent. Acknowledgments -The authors’ research on HEV is supported with grants from the Project PlantaSYST under the Widening Program, H2020 as well as under the UK Biotechnological and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Grant ‘Understanding and Exploiting Plant and Microbial Secondary Metabolism’ (BB/J004596/1). The authors want to thank Prof. George Lomonossoff (JIC, Norwich, UK) for his contribution.

Keywords: hepatitis E virus, plant molecular farming, transient expression, vaccines

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Authors: Sujatha Shanmugasundaram

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Background: It has been since one year that COVID-19 has emerged into the world. Since then, healthcare professionals facing a great challenge in to fight against this deadly virus. According to World Health Organization (WHO) 2021, it is estimated that more than 131 million confirmed cases and 2million deaths around the world due to this pandemic. Nurses are the frontline workers who play a major role in safeguarding the lives of the people in acute care settings. Evidence suggests that there are numbers of research have been carried out on nurses' and healthcare provider’s experiences during the pandemic. But, unfortunately, there are no or little evidence available on Muslim nurse’s perspective. Hence, this research will investigate the experiences of Muslim nurses working in an acute care setting during the pandemic. Purpose: The purpose of the study is to explore the experiences of Muslim nurses working in an acute setting during the COVID-19 pandemic. Research Methods: A qualitative research approach will be utilized for the study. Semi-structured interview schedule will be used to collect the data. Face to face interviews will be conducted. All interviews will be conducted in Arabic, and it will be audio recorded. Verbatim will be noted. Muslim nurses working in an acute setting will be included in the study. Convenient sampling technique will be used to recruit the participants. Ethical approval will be obtained from the study sites. Strauss and Corbin's thematic analysis will be used to analyze the data. Conclusion: Considering that nurses are the frontline workers, they have a significant role in dealing with this COVID-19. It is a great challenge for the nurses working in an acute care setting. Thus, this study will bring out significant findings that will impact the nursing practice.

Keywords: acute care, COVID-19, experiences, muslim nurses

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Authors: Parul Johri, Mala Trivedi

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Major Intrinsic proteins (MIPs), actively involved in the passive transport of small polar molecules across the membranes of almost all living organisms. MIPs that specifically transport water molecules are named aquaporins (AQPs). The permeability of membranes is actively controlled by the regulation of the amount of different MIPs present but also in some cases by phosphorylation and dephosphorylation of the channel. Based on sequence similarity, MIPs have been classified into many categories. All of the proteins are made up of the 20 amino acids, the only difference is there in their orientations. Again all the 20 amino acids are made up of the basic five elements namely: carbon, hydrogen, oxygen, sulphur and nitrogen. These elements are responsible for giving the amino acids the properties of hydrophilicity/hydrophobicity which play an important role in protein interactions. The hydrophobic amino acids characteristically have greater number of carbon atoms as carbon is the main element which contributes to hydrophobic interactions in proteins. It is observed that the carbon level of proteins in different species is different. In the present work, we have taken a sample set of 150 aquaporins proteins from Uniprot database and a dynamic programming code was written to calculate the carbon percentage for each sequence. This carbon percentage was further used to barcode the aqauporins of animals and plants. The protein taken from Oryza sativa, Zea mays and Arabidopsis thaliana preferred to have carbon percentage of 31.8 to 35, whereas on the other hand sequences taken from Mus musculus, Saccharomyces cerevisiae, Homo sapiens, Bos Taurus, and Rattus norvegicus preferred to have carbon percentage of 31 to 33.7. This clearly demarks the carbon range in the aquaporin proteins from plant and animal origin. Hence the atom level analysis of protein sequences can provide us with better results as compared to the residue level comparison.

Keywords: aquaporins, carbon, dynamic prgramming, MIPs

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Authors: Jin Hwan Cheong, Mina Hwang, Myung Hoon Han, Je Il Ryu, Young ha Oh, Seong Ho Koh, Wu Duck Won, Byung Jin Ha

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Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been reported to play critical roles in the proliferation of various cancer cells. However, the roles of LGR5 in brain tumors and the specific intracellular signaling proteins directly associated with it remain unknown. Expression of LGR5 was first measured in normal brain tissue, meningioma, and pituitary adenoma of humans. To identify the downstream signaling pathways of LGR5, siRNA-mediated knockdown of LGR5 was performed in SH-SY5Y neuroblastoma cells followed by proteomics analysis with 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). In addition, the expression of LGR5-associated proteins was evaluated in LGR5-inꠓhibited neuroblastoma cells and in human normal brain, meningioma, and pituitary adenoma tissue. Proteomics analysis showed 12 protein spots were significantly different in expression level (more than two-fold change) and subsequently identified by peptide mass fingerprinting. A protein association network was constructed from the 12 identified proteins altered by LGR5 knockdown. Direct and indirect interactions were identified among the 12 proteins. HSP 90-beta was one of the proteins whose expression was altered by LGR5 knockdown. Likewise, we observed decreased expression of proteins in the hnRNP subfamily following LGR5 knockdown. In addition, we have for the first time identified significantly higher hnRNP family expression in meningioma and pituitary adenoma compared to normal brain tissue. Taken together, LGR5 and its downstream sigꠓnaling play critical roles in neuroblastoma and brain tumors such as meningioma and pituitary adenoma.

Keywords: LGR5, neuroblastoma, meningioma, pituitary adenoma, hnRNP

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Authors: Satoshi Furukawa, Satomu Morita, Katsuji Nishi, Masahito Hitosugi

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Coronary artery dissection leading to acute myocardial infarction after blunt chest trauma is extremely rare. A 67-year-old woman suffered blunt chest trauma following a traffic accident. The electrocardiogram revealed acute posterior ST-segment elevation and myocardial infarction and coronary angiography demonstrated acute right coronary artery dissection. Following the death of the victim an autopsy was performed after cardiopulmonary support had been carried out. In this case report, we describe the case of a woman with blunt chest trauma, who developed an acute myocardial infarction secondary to right coronary artery dissection. Although there was additional the blunt chest trauma due to chest compression, we confirmed the injury at autopsy and by histological findings.

Keywords: blunt chest trauma, right coronary artery dissection, coronary angiography, autopsy, histological examination

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Authors: Kristel Dame Bañez Sumagaysay, Marie Victoria Cruz-javier

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The current subject is a case of a 21 year-old woman at 29 1/7 weeks of gestation with Pre-B cell Acute Lymphoblastic Leukemia who was admitted to the coronary care unit (CCU) of the St. Luke’s Medical Center-Global City for Severe Acute Respiratory Distress Syndrome (ARDS) secondary to hospital-acquired pneumonia secondary to pneumocystis jiroveci; central line-associated bloodstream infection (E. aerogenes). She presented with chronic hypoxemia caused by Pulmonary edema, probably secondary to heart failure secondary to cardiomyopathy chemotherapy-induced. Due to worsening feto-maternal status, extracorporeal membrane oxygenation (ECMO) for respiratory support was instituted, and an elective cesarean section was done due to multiple maternal factors and deteriorating health status under total intravenous anesthesia assisted by veno-venous extracorporeal membrane oxygenation. She delivered a live preterm newborn male, APGAR Score: 1, 0, 0, birth weight 985 grams, birth length: 40.5cm, small for gestational age.

Keywords: extracorporeal membrane oxygenation, pre-b cell acute lymphoblastic leukemia, severe acute respiratory distress syndrome, ethical dilemmas

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