Search results for: metabolic pathways
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1303

Search results for: metabolic pathways

493 Role of Human Wharton’s Jelly Mesenchymal Stem Cells Conditioned Media in Alleviating Kidney Injury via Inhibition of Renin-Angiotensin System in Diabetic Nephropathy

Authors: Pardis Abolghasemi, Benyamin Hatamsaz

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Background: Diabetic nephropathy is a serious health problem described by specific kidney structure and functional disturbance. Renoprotective effects of the stem cells secretase have been shown in many kidney diseases. The aim is to evaluate the capability of human Wharton’s jelly mesenchymal stem cells conditioned media (hWJMSCs-CM) to alleviate DN in streptozotocin (STZ)-induced diabetes. Methods: Diabetic nephropathy was induced by injection of STZ (60 mg/kg, IP) in twenty rats. Conditioned media was extracted from hWJMSCs at third passages. At week 8, diabetic rats were divided into two groups: treated (hWJMSCs-CM, 500 μl/rat for three weeks, IP) and not treated (DN). In the 11th week, three groups (control, DN and DN+hWJMSCs-CM) were kept in metabolic cages and urine was collected for 24h. Blood pressure (BP) and heart rate (HR) were continuously recorded. The serum samples were maintained for measuring BUN, Cr and angiotensin-converting enzyme (ACE) activity. The left kidney was kept at -80°C for ACE activity assessment. The right kidney and pancreas were used for histopathologic evaluation. Result: Diabetic nephropathy was detected by microalbuminuria and increased albumin/creatinine ratio, as well as the pancreas and renal structural disturbance. Glomerular filtration rate, BP and HR increased in the DN group. The ACE activity was elevated in the serum and kidneys of the DN group. Administration of hWJMSCs-CM modulated the renal functional and structural disturbance and decreased the ACE activity. Conclusion: Conditioned media was extracted from hWJMSCs may have a Renoprotective effect in diabetic nephropathy. This may happen through regulation of ACE activity and renin-angiotensin system inhibition.

Keywords: diabetic nephropathy, mesenchymal stem cells, immunomodulation, anti-inflammation

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492 Phytoremediation of Textile Wastewater Laden with 1,4-Dioxane Using Eichhornia crassipes: A Sustainable Development Approach

Authors: Hadeer Ibrahiem, Mahmoud Nasr, Masarrat M. M. Migahid, Mohamed A. Ghazy

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The release of textile wastewater loaded with 1,4 dioxane into aquatic ecosystems has been associated with various human health risks and adverse environmental impacts. In parallel, phytoremediation has been recently employed to treat highly polluted wastewater because various plant species tend to produce certain enzymes as a defense mechanism against a toxic environment. To our best knowledge, this study is the first to investigate the ability of phytoremediation using Eichhornia crassipes for the removal of various pollutants, including 1,4 dioxane, from textile wastewater. A phytoremediation system composed of Eichhornia crassipes was acclimatized for 10 d, and then operated in four lab-scale hydroponic systems, viz., negative control, positive control, and two different 1,4 dioxane concentration (400 and 500 mg/L). After 11 d of operation, the phytoremediation system achieved removal efficiencies of 67.5±3.4%, 89.4±4.4%, 83.6±3.8% for 1,4 dioxane (at initial concentration 400 mg/L), chemical oxygen demand (COD) (at initial concentration 679 mg/L), and cumulative heavy metals, respectively. The removal of these pollutants was mainly supported by the phyto-sorption and phytodegradation mechanisms. The economic feasibility of this phytoremediation system was validated by estimating the capital and operating costs, requiring 4.6 USD for the treatment of 1 m3 textile wastewater. The study concluded that the phytoremediation process could be used as a practical and economical approach to treat textile wastewater laden with various organic and inorganic pollutants. Due to the observed pollution reduction and human health protection, the study objectives would fulfill the targets of SDG 3 “Good Health and Well-being” and SDG 6 “Clean Water and Sanitation”. Further studies are required to (i) investigate the ability of plant species to withstand higher concentrations of 1,4 dioxane for an extended operation time and (ii) understand the biochemical pathways for the degradation of 1,4 dioxane via the action of plant enzymes and the associated microbial community.

Keywords: 1, 4 dioxane concentrations, hydrophytes, Eichhornia crassipes, phytoremediation effectiveness, SDGs, textile industrial effluent

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491 Type 2 Diabetes Mellitus Among a St. Lucian Population: What We Know about Lifestyle Modification

Authors: Bradley Fevrier

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Background: Type 2 diabetes mellitus, a non-communicable metabolic disorder, is a fast-growing problem for health, as it presents numerous complications and death worldwide. St. Lucia, much like most other emerging nation in the Caribbean, struggles with the management of type 2 diabetes mellitus (T2DM) among its populace. Good knowledge, attitude, and practices [KAP] of T2DM are essential in the prevention and management of this disease.Lifestyle adaptation, including increased knowledge, positive attitude, and efficient practice towards lifestyle modifications, can avert the advancement of difficulties associated with diabetes. Methods: An institutional-based cross-sectional study was conducted during the period June 15, 2022, to July15 2022. Data were collected by using the self-administered questionnaire designed to collect the required information from participants, and the data wasanalyzed using the statistical package for social science (SPSS) version 26. Knowledge, attitude, and practice of lifestyle modification among participants were determined using descriptive statistics. Results: A total of 402 participants completed the study, fully yielding an 84% response rate. Overall, the assessed levels of KAP relating to the life-threatening complications of T2DM were moderate. Results further indicated that women outnumbered men 68.4% to 31.6%, respectively. Significant positive correlation (r= 0.244, p<0.001) and (r=.203, p<0.001) were found between the knowledge level as well as the attitude level of study respondents. Conclusion: The overall study findings regarding the level of knowledge and attitude concerning lifestyle modifications among study participants were interpreted as generally high. However, the practice of healthy lifestyle modification habits was poor. The current findings suggest a need for structured educational campaigns prioritizing the importance of lifestyle modifications (weight loss, smoking cessation, physical exercise) to the general population.

Keywords: Diabetes, knowledge, lifestyle, survey

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490 Determining the Extent and Direction of Relief Transformations Caused by Ski Run Construction Using LIDAR Data

Authors: Joanna Fidelus-Orzechowska, Dominika Wronska-Walach, Jaroslaw Cebulski

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Mountain areas are very often exposed to numerous transformations connected with the development of tourist infrastructure. In mountain areas in Poland ski tourism is very popular, so agricultural areas are often transformed into tourist areas. The construction of new ski runs can change the direction and rate of slope development. The main aim of this research was to determine geomorphological and hydrological changes within slopes caused by ski run constructions. The study was conducted in the Remiaszów catchment in the Inner Polish Carpathians (southern Poland). The mean elevation of the catchment is 859 m a.s.l. and the maximum is 946 m a.s.l. The surface area of the catchment is 1.16 km2, of which 16.8% is the area of the two studied ski runs. The studied ski runs were constructed in 2014 and 2015. In order to determine the relief transformations connected with new ski run construction high resolution LIDAR data was analyzed. The general relief changes in the studied catchment were determined on the basis of ALS (Airborne Laser Scanning ) data obtained before (2013) and after (2016) ski run construction. Based on the two sets of ALS data a digital elevation models of differences (DoDs) was created, which made it possible to determine the quantitative relief changes in the entire studied catchment. Additionally, cross and longitudinal profiles were calculated within slopes where new ski runs were built. Detailed data on relief changes within selected test surfaces was obtained based on TLS (Terrestrial Laser Scanning). Hydrological changes within the analyzed catchment were determined based on the convergence and divergence index. The study shows that the construction of the new ski runs caused significant geomorphological and hydrological changes in the entire studied catchment. However, the most important changes were identified within the ski slopes. After the construction of ski runs the entire catchment area lowered about 0.02 m. Hydrological changes in the studied catchment mainly led to the interruption of surface runoff pathways and changes in runoff direction and geometry.

Keywords: hydrological changes, mountain areas, relief transformations, ski run construction

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489 Laboratory Scale Purification of Water from Copper Waste

Authors: Mumtaz Khan, Adeel Shahid, Waqas Khan

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Heavy metals presence in water streams is a big danger for aquatic life and ultimately effects human health. Removal of copper (Cu) by ispaghula husk, maize fibre, and maize oil cake from synthetic solution in batch conditions was studied. Different experimental parameters such as contact time, initial solution pH, agitation rate, initial Cu concentration, biosorbent concentration, and biosorbent particle size has been studied to quantify the Cu biosorption. The rate of adsorption of metal ions was very fast at the beginning and became slow after reaching the saturation point, followed by a slower active metabolic uptake of metal ions into the cells. Up to a certain point, (pH=4, concentration of Cu = ~ 640 mg/l, agitation rate = ~ 400 rpm, biosorbent concentration = ~ 0.5g, 3g, 3g for ispaghula husk, maize fiber and maize oil cake, respectively) increasing the pH, concentration of Cu, agitation rate, and biosorbent concentration, increased the biosorption rate; however the sorption capacity increased by decreasing the particle size. At optimized experimental parameters, the maximum Cu biosorption by ispaghula husk, maize fibre and maize oil cake were 86.7%, 59.6% and 71.3%, respectively. Moreover, the results of the kinetics studies demonstrated that the biosorption of copper on ispaghula husk, maize fibre, and maize oil cake followed pseudo-second order kinetics. The results of adsorption were fitted to both the Langmuir and Freundlich models. The Langmuir model represented the sorption process better than Freundlich, and R² value ~ 0.978. Optimizations of physical and environmental parameters revealed, ispaghula husk as more potent copper biosorbent than maize fibre, and maize oil cake. The sorbent is cheap and available easily, so this study can be applied to remove Cu impurities on pilot and industrial scale after certain modifications.

Keywords: biosorption, copper, ispaghula husk, maize fibre, maize oil cake, purification

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488 Investigating the Potential Use of Unsaturated Fatty Acids as Antifungal Crop Protective Agents

Authors: Azadeh Yasari, Michael Ganzle, Stephen Strelkov, Nuanyi Liang, Jonathan Curtis, Nat N. V. Kav

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Pathogenic fungi cause significant yield losses and quality reductions to major crops including wheat, canola, and barley. Toxic metabolites produced by phytopathogenic fungi also pose significant risks to animal and human health. Extensive application of synthetic fungicides is not a sustainable solution since it poses risks to human, animal and environmental health. Unsaturated fatty acids may provide an environmentally friendly alternative because of their direct antifungal activity against phytopathogens as well as through the stimulation of plant defense pathways. The present study assessed the in vitro and in vivo efficacy of two hydroxy fatty acids, coriolic acid and ricinoleic acid, against the phytopathogens Fusarium graminearum, Pyrenophora tritici-repentis, Pyrenophora teres f. teres, Sclerotinia sclerotiorum, and Leptosphaeria maculans. Antifungal activity of coriolic acid and ricinoleic acid was evaluated using broth micro-dilution method to determine the minimum inhibitory concentration (MIC). Results indicated that both ricinoleic acid and coriolic acid showed antifungal activity against phytopathogens, with the strongest inhibitory activity against L. maculans, but the MIC varied greatly between species. An antifungal effect was observed for coriolic acid in vivo against pathogenic fungi of wheat and barley. This effect was not correlated to the in vitro activity because ricinoleic acid with equivalent in vitro antifungal activity showed no protective effect in vivo. Moreover, neither coriolic acid nor ricinoleic acid controlled fungal pathogens of canola. In conclusion, coriolic acid inhibits some phytopathogens in vivo and may have the potential to be an effective crop protection agent.

Keywords: coriolic acid, minimum inhibitory concentration, pathogenic fungi, ricinoleic acid

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487 Disruption of MoNUC1 Gene Mediates Conidiation in Magnaporthe oryzae

Authors: Irshad Ali Khan, Jian-Ping Lu, Xiao-Hong Liu, Fu-Cheng Lin

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This study reports the functional analysis of a gene MoNUC1 in M. oryzae, which is homologous to the Saccharomyces cerevisiae NUC1 encoding a mitochondrial nuclease protein. The MoNUC1 having a gene locus MGG_05324 is 1002-bp in length and encodes an identical protein of 333 amino acids. We disrupted the gene through gene disruption strategy and isolated two mutants confirmed by southern blotting. The deleted mutants were then used for phenotypic studies and their phenotypes were compared to those of the Guy-11 strain. The mutants were first grown on CM medium to find the effect of MoNUC1 gene disruption on colony growth and the mutants were found to show normal culture colony growth similar to that of the Guy-11 strain. Conidial germination and appressorial formation were also similar in both the mutants and Guy-11 strains showing that this gene plays no significant role in these phenotypes. For pathogenicity, the mutants and Guy-11 mycelium blocks were inoculated on blast susceptible barley seedlings and it was found that both the strains exhibited full pathogenicity showing coalesced and necrotic blast lesions suggesting that this gene is not involved in pathogenicity. Mating of the mutants with 2539 strain formed numerous perithecia showing that MoNUC1 is not essential for sexual reproduction in M. oryzae. However, the mutants were found to form reduced conidia (1.06±8.03B and 1.08±9.80B) than those of the Guy-11 strain (1.46±10.61A) and we conclude that this protein is not required for the blast fungus to cause pathogenicity but plays significant role in conidiation. Proteins of signal transduction pathways that could be disrupted/ intervened genetically or chemically could lead to antifungal products of important fungal cereal diseases and reduce rice yield losses. Tipping the balance toward understanding the whole of pathogenesis, rather than simply conidiation will take some time, but clearly presents the most exciting challenge of all.

Keywords: appressorium formation, conidiation, NUC1, Magnaporthe oryzae, pathogenicity

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486 Determinants of Child Malnutrition in Sub-Saharan Africa

Authors: Habtamu Fufa, Yemane Berhane

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Child under nutrition has long-term consequences for intellectual ability, economic productivity, reproductive performance and susceptibility to metabolic and cardiovascular disease. The unacceptably high prevalence of malnutrition in young children of the region has not changed much over the last decades, which could make the achievement of the corresponding Millennium Development Goals very unlikely. Despite the well-documented problems of child malnutrition in Sub-Saharan Africa, there is few systematic review of evidences on determinants of child malnutrition in the region. The current available evidence on determinants of child under nutrition in Sub-Saharan Africa is systematically reviewed. The method used in searching relevant literature was using bio medical databases PUBMED, Google scholar and the website of the World Health Organization on nutrition using the following key words: "Determinants “, "Child Malnutrition", and "Sub- Saharan Africa". The search was limited to articles published in and after 1995 up to date. In all the reviewed articles, the data were analyzed using multivariate regression analysis and or odds ratios for significance of determinants in child malnutrition. Synthesis of 40 published articles from various countries of the region is done and noted that household economic status, maternal education, disease, breastfeeding practices, age and sex of a child, birth interval and residential areas were found to be determinants of child under nutrition. Poverty remains the main factor of malnutrition in Sub-Saharan Africa and poor education of parents aggravates the malnutrition through perpetuation of poor nutrition practices. Male children under five years are the most affected ones. Understanding of these determinants of poor nutritional attainment would provide insights in designing interventions for reducing the high levels of child malnutrition in this region. Large-scale multi-sectoral community-based interventions are urgently needed for a sustainable improvement of child nutritional & health status in Sub-Saharan Africa.

Keywords: child malnutrition, determinants, Sub-Saharan Africa, health status

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485 A Perspective on Emergency Care of Gunshot Injuries in Northern Taiwan

Authors: Liong-Rung Liu, Yu-Hui Chiu, Wen-Han Chang

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Firearm injuries are high-energy injuries. The ballistic pathways could cause severe burns or chemical damages to vessels, musculoskeletal or other major organs. The high mortality rate is accompanied by complications such as sepsis. As laws prohibit gun possession, civilian gunshot wounds (GSW) are relatively rare in Taiwan. Our hospital, Mackay Memorial Hospital, located at the center of Taipei city is surrounded by nightclubs and red-light districts. Due to this unique location, our hospital becomes the first-line trauma center managing gunshot victims in Taiwan. To author’s best knowledge, there are few published research articles regarding this unique situation. We hereby analyze the distinct characteristics and length of stay (LOS) of GSW patients in the emergency room (ER) at Mackay Memorial Hospital. A 6-year retrospective analysis of 27 patients treated for GSW injuries from January 2012 to December 2017 was performed. The patients’ records were reviewed for the following analyses, 1) wound position and the correlated clinical presentations; 2) the LOS in ED of patients receiving emergency surgery for major organ or vascular injuries. We found males (96.3%) were injured by guns more often than females (3.7%) in all age groups. The most common injured site was in the extremities. With regards to the ER LOS, the average time were 72.2 ± 34.5 minutes for patients with triage I and 207.4 ± 143.9 minutes for patients with triage II. The ED LOS of patients whose ISS score were more than 15 was 59.9 ± 25.6 minutes, and 179.4 ± 119.8 minutes for patients whose ISS score were between 9 to 15, respectively. Among these 27 patients, 10 patients had emergency surgery and their average ED stay time was 104.5 ± 33.3 minutes. Even more, the average ED stay time could be shortened to 88.8 ± 32.3 minutes in the 5 patients with trauma team activation. In conclusion, trauma team activation in severe GSW patients indeed shortens the ED LOS and might initially improve the quality of patient care. This is the result of better trauma systems, including advances in care from emergency medical services and acute care surgical management.

Keywords: gunshot, length of stay, trauma, mortality

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484 Investigating the Flavin-Dependent Thymidylate Synthase (FDTS) Enzyme from Clostridioides Difficile (C. diff)

Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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483 The Effect of High Intensity by Intervals Training on Plasma Interleukin 13 and Insulin Resistance in Patients with Attention Deficit Hyperactivity Disorder (ADHD)

Authors: Goodarzvand Fatemeh, Soori Rahman, Effatpanah Mohammad, Ajbarnejad Ali

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Attention deficit hyperactivity disorder (ADHD) is characterized by a pervasive pattern of developmentally inappropriate inattentive, impulsive and hyperactive behaviors that typically begin during the preschool ages and often persist into adulthood. This disorder is related to autism and schizophrenia and other psychological disorders and clinical conditions such as insulin resistance and they may operate through common pathways, and treatments used exclusively for one of these conditions may prove beneficial for the others. While ADHD is not fully understood as developmental disorder with an etiopathogeny, but studies show that core symptom of disorder was associated with and increased by the interleukins IL-13, where relation of IL-13 with inattention was notable. Regular exercise improves functions associated with attention deficit hyperactivity disorder (ADHD). However, the impact of exercise on cytokines associated with the disease activity remains relatively unexplored. The aim of this study was to examine the effects of 6 weeks high intensity by intervals training (HIIT) on IL-13 levels and insulin resistance in boys with ADHD. Twenty eight boys with ADHD disease in a range of 12-18 year of old participated in this study as the subject. Subjects were divided into control group (n=10) and training group (n=18) randomly. The training group performed progressive HIIT program, 3 days a week for 6 weeks. The control group was in absolute rest at the same time. The results showed that after six weeks of HIIT, IL-13 decreased in the exercise group and these changes achieved (p= 0.002) statistical significance (p < 0.005). The results suggest HIIT with specific intensity and duration utilized in this study had not significant effect on insulin resistance levels in female patients with ADHD (p=0.39), while the difference in the average control and case group was decreased.

Keywords: attention deficit hyperactivity disorder, interleukin 13, insulin resistance, high intensity by intervals training

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482 Real Time PCR Analysis of microRNA Expression in Oral Cancer

Authors: Karl Kingsley

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Many mechanisms are involved in the control of cellular differentiation and growth, which are often dysregulated in many cancers. Many distinct pathways are involved in these mechanisms of control, including deoxyribonuclease (DNA) methyltransferase and histone deacetylase (HDAC) activation that controls both genetic and epigenetic modifications and micro ribonucleic acid (RNA) expression. Less is known about the expression of DNA methyltransferase (DNMT) and HDAC in oral cancers and the effect on microRNA expression. The primary objective of this study was to evaluate the expression of DNMT and HDAC family members in oral cancer and the concomitant expression of cancer-associated microRNAs. Using commercially available oral cancers, including squamous cell carcinoma (SCC)-4, SCC-9, SCC-15, and SCC-25, RNA was extracted and screened for DNMT, HDAC, and microRNA expression using highly-specific primers and quantitative polymerase chain reaction (qPCR). These data revealed low or absent expression of DNMT-1, which is associated with cellular differentiation but increased expression of DNMT-3a and DNMT-3b in all SCC cell lines compared with normal non-cancerous cell controls. In addition, no expression of HDAC1 and HDAC2 expression was found among the normal, non-cancerous cells but was highly expressed in each of the SCC cell lines examined. Differential expression of oncogenic and cancer-associated microRNAs was also observed among the SCC cell lines, including miR-21, miR-133, miR-149, miR-155, miR-365, and miR-720. These findings also appeared to vary according to observed growth rates among these cells. These data may be the first to demonstrate the expression and association between HDAC and DNMT3 family members among oral cancers. In addition, the differential expression of these epigenetic modifiers may be associated with the expression of specific microRNAs in these cancers, which have not previously been observed to the best of the author's knowledge. In addition, some associations and relationships may exist between the expression of these biomarkers and the rates of growth and proliferation, which may suggest that these expression patterns might represent potentially useful biomarkers to determine tumor aggressiveness and other phenotypic behaviors among oral cancers.

Keywords: oral cancer, DNA methyltransferase, histone deacetylase, microRNA

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481 Mediation Analysis of the Efficacy of the Nimotuzumab-Cisplatin-Radiation (NCR) Improve Overall Survival (OS): A HPV Negative Oropharyngeal Cancer Patient (HPVNOCP) Cohort

Authors: Akshay Patil

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Objective: Mediation analysis identifies causal pathways by testing the relationships between the NCR, the OS, and an intermediate variable that mediates the relationship between the Nimotuzumab-cisplatin-radiation (NCR) and OS. Introduction: In randomized controlled trials, the primary interest is in the mechanisms by which an intervention exerts its effects on the outcomes. Clinicians are often interested in how the intervention works (or why it does not work) through hypothesized causal mechanisms. In this work, we highlight the value of understanding causal mechanisms in randomized trial by applying causal mediation analysis in a randomized trial in oncology. Methods: Data was obtained from a phase III randomized trial (Subgroup of HPVNOCP). NCR is reported to significantly improve the OS of patients locally advanced head and neck cancer patients undergoing definitive chemoradiation. Here, based on trial data, the mediating effect of NCR on patient overall survival was systematically quantified through progression-free survival(PFS), disease free survival (DFS), Loco-regional failure (LRF), and the disease control rate (DCR), Overall response rate (ORR). Effects of potential mediators on the HR for OS with NCR versus cisplatin-radiation (CR) were analyzed by Cox regression models. Statistical analyses were performed using R software Version 3.6.3 (The R Foundation for Statistical Computing) Results: Effects of potential mediator PFS was an association between NCR treatment and OS, with an indirect-effect (IE) 0.76(0.62 – 0.95), which mediated 60.69% of the treatment effect. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.64 (95% CI: 0.43 – 0.96; P=0.03). The DFS was also a significant mediator and had an IE 0.77 (95% CI; 0.62-0.93), 58% mediated). Smaller mediation effects (maximum 27%) were observed for LRF with IE 0.88(0.74 – 1.06). Both DCR and ORR mediated 10% and 15%, respectively, of the effect of NCR vs. CR on the OS with IE 0.65 (95% CI; 0.81 – 1.08) and 0.94(95% CI; 0.79 – 1.04). Conclusion: Our findings suggest that PFS and DFS were the most important mediators of the OS with nimotuzumab to weekly cisplatin-radiation in HPVNOCP.

Keywords: mediation analysis, cancer data, survival, NCR, HPV negative oropharyngeal

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480 Alpha Lipoic Acid: An Antioxidant for Infertility

Authors: Chiara Di Tucci, Giulia Galati, Giulia Mattei, Valentina Bonanni, Oriana Capri, Renzo D'Amelio, Ludovico Muzii, Pierluigi Benedetti Panici

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Objective: Infertility is an increasingly frequent health condition, which may depend on female or male factors. Oxidative stress (OS), resulting from a disrupted balance between reactive oxygen species (ROS) and protective antioxidants, affects the reproductive lifespan of men and women. In this review, we examine if alpha lipoic acid (ALA), among the oral supplements currently in use, has an evidence-based beneficial role in the context of female and male infertility. Methods: We performed a search from English literature using the PubMed database with the following keywords: 'female infertility', 'male infertility', 'semen', 'sperm', 'sub-fertile man', 'alpha-lipoic acid', ' alpha lipoic acid', 'lipoid acid', 'endometriosis', 'chronic pelvic pain', 'follicular fluid' and 'oocytes'. We included clinical trials, multicentric studies, and reviews. The total number of references found after automatically and manually excluding duplicates was 180. After the primary and secondary screening, 28 articles were selected. Results: The available literature demonstrates the positive effects of ALA in multiple processes, from oocyte maturation (0.87 ± 0.9% of oocyte in MII vs 0.81 ± 3.9%; p < .05) to fertilization, embryo development (57.7% vs 75.7% grade 1 embryo; p < .05) and reproductive outcomes. Its regular administration both in sub-fertile women and men has been shown to reduce pelvic pain in endometriosis (p < .05), regularize menstrual flow and metabolic disorders (p < .01), and improve sperm quality (p < .001). Conclusions: ALA represents a promising new molecule in the field of couple infertility. More clinical studies are needed in order to enhance its use in clinical practice.

Keywords: alpha lipoic acid, endometriosis, infertility, male factor, polycystic ovary syndrome

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479 Re-Differentiation Effect of Sesquiterpene Farnesol on De-Differentiated Rabbit Chondrocytes

Authors: Chun Hsien Wu, Guan Xuan Wu, Hsia Ying Cheng, Shyh Ming Kuo

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Articular cartilage is composed of chondrocytes and extracellular matrix, such as collagen fibers, glycosaminoglycans, etc., which play an important role in lubricating and cushion joint activities. The phenotypic expression and metabolic activity of chondrocytes are extremely important in maintaining the functions of articular cartilage. In in vitro passaged culture of chondrocytes, chondrocytes gradually lose their original cell phenotype and morphology, which is called dedifferentiation. After continuous passaged culture of chondrocytes or induction by inflammatory factor IL-1, chondrocytes changed their phenotype and morphology. Also, the extracellular matrix type II collagen and GAG secretion were significantly reduced, while type I and X collagen were synthesized. Farnesol is an anti-inflammatory and antioxidant sesquiterpene compound that has the specific property of promoting collagen production. The purpose of this study was to investigate whether farnesol could restore the original type II collagen synthesis and, furthermore, the mechanisms of farnesol on the synthesis of type II collagen from the de-differentiated chondrocytes. The obtained results showed that the de-differentiated chondrocytes significantly restored to secret type II collagen and GAG (2.5-folds increases), and the secretion of collagen I and X and PGE2 synthesis were also significantly reduced after being treated with farnesol, indicating that farnesol had a restoration/re-differentiation effect on de-differentiated chondrocytes. The de-differentiated chondrocytes exhibited decreased expression of PPAR-γ and upregulated TGF-β expression to increase the MMP-13 expression. Higher expression of MMP-13 caused chondrocytes to secret type X collagen. On the contrary, increasing the expression of PPAR-γ would benefit the production of type II collagen. As shown, the PPAR-γ expression increased, and MMP-13 expression decreased after being treated with farnesol, indicating a possible signal pathway of farnesol to restore the production of type II collagen. However, more detailed mechanisms still need to evaluate.

Keywords: chondrocytes, de-differentiation, farnesol, re-differentiation

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478 The Impact of Centralisation on Radical Prostatectomy Outcomes: Our Outcomes

Authors: Jemini Vyas, Oluwatobi Adeyoe, Jenny Branagan, Chandran Tanabalan, John Beatty, Aakash Pai

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Introduction: The development of robotic surgery has accelerated centralisation to tertiary centres, where robotic radical prostatectomy (RP) is offered. The purpose of concentrating treatment in high volume specialist centres is to improve the quality of care and patient outcomes. The aim of this study was to assess the impact on clinical outcomes of centralisation for locally diagnosed patients undergoing RP. Methods: Clinical outcomes for 169 consecutive laparoscopic & open RP pre-centralisation were retrospectively compared with 50 consecutive robotic RP conducted over a similar period post-centralisation. Preoperative risk stratification and time to surgery were collected. Perioperative outcomes, including length of stay (LOS) and complications, were collated. Post-operative outcomes, including erectile dysfunction (ED), biochemical recurrence (BCR), and urinary continence, were assessed. Results: Preoperative risk stratification showed no difference between the two groups. The median time from diagnosis to treatment was similar between the two groups (pre-centralisation, 121 days, post-centralisation, 117 days). The mean length of stay (pre-centralisation, 2.1 days, post-centralisation, 1.6 days) showed no significant difference (p=0.073). Proportion of overall complications (pre-centralisation, 11.4%, post-centralisation, 8.7%) and complications, above Clavien-Dindo 2, were similar between the two groups (pre-centralisation1.2%, post-centralisation 2.2%). Post operative functional parameters, including continence and ED, were comparable. Five-year BCR free rate was 78% for the pre-centralisation group and 79% for the post centralisation group. Conclusion: For our cohort of patients, clinical outcomes have remained static during centralisation. It is imperative that centralisation is accompanied by increased capacity, streamlining of pathways, and training to ensure that improved quality of care is achieved. Our institution has newly acquired a robot, and prospectively studying this data may support the reversal of centralisation for RP surgery.

Keywords: prostate, cancer, prostatectomy, clinical

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477 Traumatic Chiasmal Syndrome Following Traumatic Brain Injury

Authors: Jiping Cai, Ningzhi Wangyang, Jun Shao

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Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality that leads to structural and functional damage in several parts of the brain, such as cranial nerves, optic nerve tract or other circuitry involved in vision and occipital lobe, depending on its location and severity. As a result, the function associated with vision processing and perception are significantly affected and cause blurred vision, double vision, decreased peripheral vision and blindness. Here two cases complaining of monocular vision loss (actually temporal hemianopia) due to traumatic chiasmal syndrome after frontal head injury were reported, and were compared the findings with individual case reports published in the literature. Reported cases of traumatic chiasmal syndrome appear to share some common features, such as injury to the frontal bone and fracture of the anterior skull base. The degree of bitemporal hemianopia and visual loss acuity have a variable presentation and was not necessarily related to the severity of the craniocerebral trauma. Chiasmal injury may occur even in the absence bony chip impingement. Isolated bitemporal hemianopia is rare and clinical improvement usually may not occur. Mechanisms of damage to the optic chiasm after trauma include direct tearing, contusion haemorrhage and contusion necrosis, and secondary mechanisms such as cell death, inflammation, edema, neurogenesis impairment and axonal damage associated with TBI. Beside visual field test, MRI evaluation of optic pathways seems to the strong objective evidence to demonstrate the impairment of the integrity of visual systems following TBI. Therefore, traumatic chiasmal syndrome should be considered as a differential diagnosis by both neurosurgeons and ophthalmologists in patients presenting with visual impairment, especially bitemporal hemianopia after head injury causing frontal and anterior skull base fracture.

Keywords: bitemporal hemianopia, brain injury, optic chiasma, traumatic chiasmal syndrome.

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476 Metabolic Profiling of Populus trichocarpa Family 1 UDP-Glycosyltransferases

Authors: Patricia M. B. Saint-Vincent, Anna Furches, Stephanie Galanie, Erica Teixeira Prates, Piet Jones, Nancy Engle, David Kainer, Wellington Muchero, Daniel Jacobson, Timothy J. Tschaplinski

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Uridine diphosphate-glycosyltransferases (UGTs) are enzymes that catalyze sugar transfer to a variety of plant metabolites. UGT substrates, which include plant secondary metabolites involved in lignification, demonstrate new activities and incorporation when glycosylated. Knowledge of UGT function, substrate specificity, and enzyme products is important for plant engineering efforts, especially related to increasing plant biomass through lignification. UGTs in Populus trichocarpa, a biofuel feedstock, and model woody plant, were selected from a pool of gene candidates using rapid prioritization strategies. A functional genomics workflow, consisting of a metabolite genome-wide association study (mGWAS), expression of synthetic codon-optimized genes, and high-throughput biochemical assays with mass spectrometry-based analysis, was developed for determining the substrates and products of previously-uncharacterized enzymes. A total of 40 UGTs from P. trichocarpa were profiled, and the biochemical assay results were compared to predicted mGWAS connections. Assay results confirmed seven of 11 leaf mGWAS associations and demonstrated varying levels of substrate specificity among candidate UGTs. P. trichocarpa UGT substrate processing confirms the role of these newly-characterized enzymes in lignan, flavonoid, and phytohormone metabolism, with potential implications for cell wall biosynthesis, nitrogen uptake, and biotic and abiotic stress responses.

Keywords: Populus, metabolite-gene associations, GWAS, bio feedstocks, glycosyltransferase

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475 Metabolic Manipulation as a Strategy for Optimization of Biomass Productivity and Oil Content in the Microalgae Desmodesmus Sp.

Authors: Ivan A. Sandoval Salazar, Silvia F. Valderrama

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The microalgae oil emerges as a promising source of raw material for many industrial applications. Thus, this study had as a main focus on the cultivation of the microalgae species Desmodesmus sp. in laboratory scale with a view to maximizing biomass production and triglyceride content in the lipid fraction. Initially, culture conditions were selected to optimize biomass production, which was subsequently subjected to nutritional stress by varying nitrate and phosphate concentrations in order to increase the content and productivity of fatty acids. The culture medium BOLD 3N, nitrate and phosphate, light intensity 250,500 and 1000 μmol photons.m².s⁻¹, photoperiod of 12:12 were evaluated. Under the best conditions of the tests, a maximum cell division of 1.13 div.dia⁻¹ was obtained on the sixth day of culture, beginning of the exponential phase, and a maximum concentration of 8.42x107 cell.mL⁻¹ and dry biomass of 3.49 gL⁻¹ on the 20th day, in the stationary phase. The lipid content in the first stage of culture was approximately 8% after 12 days and at the end of the culture in the stationary phase ranged from 12% to 16% (20 days). In the microalgae grown at 250 μmol fotons.m2.s-1 the fatty acid profile was mostly polyunsaturated (52%). The total of unsaturated fatty acids, identified in this species of microalga, reached values between 70 and 75%, being qualified for use in the food and pharmaceutical industry. In addition, this study showed that the cultivation conditions influenced mainly the production of polyunsaturated fatty acids, with the predominance of γ-linolenic acid. However, in the cultures submitted to the highest the intensity of light (1000 μmol photons.m².s⁻¹) and low concentrations of nitrate and phosphate, saturated and monounsaturated fatty acids, which present greater oxidative stability, were identified mainly (60 to 70 %) being qualified for the production of biodiesel and for oleochemistry.

Keywords: microalgae, Desmodesmus sp, fatty acids, biodiesel

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474 Brain Connectome of Glia, Axons, and Neurons: Cognitive Model of Analogy

Authors: Ozgu Hafizoglu

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An analogy is an essential tool of human cognition that enables connecting diffuse and diverse systems with physical, behavioral, principal relations that are essential to learning, discovery, and innovation. The Cognitive Model of Analogy (CMA) leads and creates patterns of pathways to transfer information within and between domains in science, just as happens in the brain. The connectome of the brain shows how the brain operates with mental leaps between domains and mental hops within domains and the way how analogical reasoning mechanism operates. This paper demonstrates the CMA as an evolutionary approach to science, technology, and life. The model puts forward the challenges of deep uncertainty about the future, emphasizing the need for flexibility of the system in order to enable reasoning methodology to adapt to changing conditions in the new era, especially post-pandemic. In this paper, we will reveal how to draw an analogy to scientific research to discover new systems that reveal the fractal schema of analogical reasoning within and between the systems like within and between the brain regions. Distinct phases of the problem-solving processes are divided thusly: stimulus, encoding, mapping, inference, and response. Based on the brain research so far, the system is revealed to be relevant to brain activation considering each of these phases with an emphasis on achieving a better visualization of the brain’s mechanism in macro context; brain and spinal cord, and micro context: glia and neurons, relative to matching conditions of analogical reasoning and relational information, encoding, mapping, inference and response processes, and verification of perceptual responses in four-term analogical reasoning. Finally, we will relate all these terminologies with these mental leaps, mental maps, mental hops, and mental loops to make the mental model of CMA clear.

Keywords: analogy, analogical reasoning, brain connectome, cognitive model, neurons and glia, mental leaps, mental hops, mental loops

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473 In silico Analysis towards Identification of Host-Microbe Interactions for Inflammatory Bowel Disease Linked to Reactive Arthritis

Authors: Anukriti Verma, Bhawna Rathi, Shivani Sharda

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Reactive Arthritis (ReA) is a disorder that causes inflammation in joints due to certain infections at distant sites in the body. ReA begins with stiffness, pain, and inflammation in these areas especially the ankles, knees, and hips. It gradually causes several complications such as conjunctivitis in the eyes, skin lesions in hand, feet and nails and ulcers in the mouth. Nowadays the diagnosis of ReA is based upon a differential diagnosis pattern. The parameters for differentiating ReA from other similar disorders include physical examination, history of the patient and a high index of suspicion. There are no standard lab tests or markers available for ReA hence the early diagnosis of ReA becomes difficult and the chronicity of disease increases with time. It is reported that enteric disorders such as Inflammatory Bowel Disease (IBD) that is inflammation in gastrointestinal tract namely Crohn’s Disease (CD) and Ulcerative Colitis (UC) are reported to be linked with ReA. Several microorganisms are found such as Campylobacter, Salmonella, Shigella and Yersinia causing IBD leading to ReA. The aim of our study was to perform the in-silico analysis in order to find interactions between microorganisms and human host causing IBD leading to ReA. A systems biology approach for metabolic network reconstruction and simulation was used to find the essential genes of the reported microorganisms. Interactomics study was used to find the interactions between the pathogen genes and human host. Genes such as nhaA (pathogen), dpyD (human), nagK (human) and kynU (human) were obtained that were analysed further using the functional, pathway and network analysis. These genes can be used as putative drug targets and biomarkers in future for early diagnosis, prevention, and treatment of IBD leading to ReA.

Keywords: drug targets, inflammatory bowel disease, reactive arthritis, systems biology

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472 Oxidative and Hormonal Disruptions Underlie Bisphenol A: Induced Testicular Toxicity in Male Rabbits

Authors: Kadry M. Sadek, Tarek K. Abouzed, Mousa A. Ayoub

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The presence of endocrine-disrupting compounds, such as bisphenol A (BPA), in the environment can cause serious health problems. However, there are controversial opinions. This study investigated the reproductive, metabolic, oxidative and immunologic-disrupting effects of bisphenol A in male rabbits. Rabbits were divided into five groups. The first four rabbit groups were administered oral BPA (1, 10, 50, or 100 mg/kg/day) for ten weeks. The fifth group was administered corn oil as the vehicle. BPA significantly decreased serum testosterone, estradiol and the free androgen index (FAI) and significantly increased sex hormone binding globulin (SHBG) compared with the placebo group. The higher doses of BPA showed a significant decrease in follicular stimulating hormone (FSH) and luteinizing hormone (LH). A significant increase in blood glucose levels was identified in the BPA groups. The non-significant difference in insulin levels is a novel finding. The cumulative testicular toxicity of BPA was clearly demonstrated by the dose-dependent decrease in absolute testes weight, primary measures of semen quality and a significant increase in testicular malonaldehyde (MDA). Moreover, BPA significantly decreased total antioxidant capacity (TAC) and significantly increased immunoglobulin G (IgG) at the highest concentration. Our results suggest that BPA, especially at higher doses, is associated with many adverse effects on metabolism, oxidative stress, immunity, sperm quality and markers of androgenic action. These results may reflect the estrogenic effects of BPA, which we hypothesize could be related, in part, to an inhibitory effect on testicular steroidogenesis. The induction of oxidative stress by BPA may play an additional role in testicular toxicity. These results suggest that BPA poses a threat to endocrine and reproductive functions.

Keywords: bisphenol A, oxidative stress, rabbits, semen quality, steroidogenesis

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471 Behavioral Effects of Oxidant and Reduced Chemorepellent on Mutant and Wild-Type Tetrahymena thermophila

Authors: Ananya Govindarajan

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Tetrahymena thermophila is a single-cell, eukaryotic organism that belongs to the Protozoa Kingdom. Tetrahymena thermophila is often used in signal transduction pathway studies because of its ability to model sensory input and the effects of environmental conditions such as chemicals and temperature. The recently discovered G37 chemorepellent receptor showed increased responsiveness to all chemorepellents. Investigating the mutant G37 Tetrahymena gene in various test solutions, including ferric chloride, ferrous sulfate, hydrogen peroxide, tetrazolium blue, potassium chloride, and dithiothreitol were performed to determine the role of oxidants and reducing agents with the mutant and wild-type cells (CU427) to assess the role of the receptor. Behavioral assays and recordings processed by ImageJ indicated that ferric chloride, hydrogen peroxide, and tetrazolium blue yielded little to no chemorepellent responses from G37 cells (<20% ARs). CU427 cells were over-responsive based on the mean percent of cells (>50% ARs). Reducing agents elicited chemorepellent responses from both G37 and CU427, in addition to potassium chloride. Cell responses were classified as over-responsive (>50% ARs). Dithiothreitol yielded unexpected results as G37 (37.0% ARs) and CU427 (38.1% ARs) had relatively similar responses and were only responsive and not over-responsive to the reducing agent test chemical solution. Ultimately, this indicates that the G37 receptor is more interactive with molecules that are reducing agents or non-oxidant compounds; G37 may be unable to sense and respond to oxidants effectively, further elucidating the pathways of the G37 strain and nature of this receptor. Results also indicate that the CSF most likely contained an oxidant, like ferric chloride. This research can be further applied to neuronal influences and how specific compounds may affect human neurons individually and their excitability as the responses model action potentials and membrane potential.

Keywords: tetrahymena thermophila, signal transduction, chemosensory, oxidant, reducing agent

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470 Industrial Prototype for Hydrogen Separation and Purification: Graphene Based-Materials Application

Authors: Juan Alfredo Guevara Carrio, Swamy Toolahalli Thipperudra, Riddhi Naik Dharmeshbhai, Sergio Graniero Echeverrigaray, Jose Vitorio Emiliano, Antonio Helio Castro

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In order to advance the hydrogen economy, several industrial sectors can potentially benefit from the trillions of stimulus spending for post-coronavirus. Blending hydrogen into natural gas pipeline networks has been proposed as a means of delivering it during the early market development phase, using separation and purification technologies downstream to extract the pure H₂ close to the point of end-use. This first step has been mentioned around the world as an opportunity to use existing infrastructures for immediate decarbonisation pathways. Among current technologies used to extract hydrogen from mixtures in pipelines or liquid carriers, membrane separation can achieve the highest selectivity. The most efficient approach for the separation of H₂ from other substances by membranes is offered from the research of 2D layered materials due to their exceptional physical and chemical properties. Graphene-based membranes, with their distribution of pore sizes in nanometers and angstrom range, have shown fundamental and economic advantages over other materials. Their combination with the structure of ceramic and geopolymeric materials enabled the synthesis of nanocomposites and the fabrication of membranes with long-term stability and robustness in a relevant range of physical and chemical conditions. Versatile separation modules have been developed for hydrogen separation, which adaptability allows their integration in industrial prototypes for applications in heavy transport, steel, and cement production, as well as small installations at end-user stations of pipeline networks. The developed membranes and prototypes are a practical contribution to the technological challenge of supply pure H₂ for the mentioned industries as well as hydrogen energy-based fuel cells.

Keywords: graphene nano-composite membranes, hydrogen separation and purification, separation modules, indsutrial prototype

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469 Disease Trajectories in Relation to Poor Sleep Health in the UK Biobank

Authors: Jiajia Peng, Jianqing Qiu, Jianjun Ren, Yu Zhao

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Background: Insufficient sleep has been focused on as a public health epidemic. However, a comprehensive analysis of disease trajectory associated with unhealthy sleep habits is still unclear currently. Objective: This study sought to comprehensively clarify the disease's trajectory in relation to the overall poor sleep pattern and unhealthy sleep behaviors separately. Methods: 410,682 participants with available information on sleep behaviors were collected from the UK Biobank at the baseline visit (2006-2010). These participants were classified as having high- and low risk of each sleep behavior and were followed from 2006 to 2020 to identify the increased risks of diseases. We used Cox regression to estimate the associations of high-risk sleep behaviors with the elevated risks of diseases, and further established diseases trajectory using significant diseases. The low-risk unhealthy sleep behaviors were defined as the reference. Thereafter, we also examined the trajectory of diseases linked with the overall poor sleep pattern by combining all of these unhealthy sleep behaviors. To visualize the disease's trajectory, network analysis was used for presenting these trajectories. Results: During a median follow-up of 12.2 years, we noted 12 medical conditions in relation to unhealthy sleep behaviors and the overall poor sleep pattern among 410,682 participants with a median age of 58.0 years. The majority of participants had unhealthy sleep behaviors; in particular, 75.62% with frequent sleeplessness, and 72.12% had abnormal sleep durations. Besides, a total of 16,032 individuals with an overall poor sleep pattern were identified. In general, three major disease clusters were associated with overall poor sleep status and unhealthy sleep behaviors according to the disease trajectory and network analysis, mainly in the digestive, musculoskeletal and connective tissue, and cardiometabolic systems. Of note, two circularity disease pairs (I25→I20 and I48→I50) showed the highest risks following these unhealthy sleep habits. Additionally, significant differences in disease trajectories were observed in relation to sex and sleep medication among individuals with poor sleep status. Conclusions: We identified the major disease clusters and high-risk diseases following participants with overall poor sleep health and unhealthy sleep behaviors, respectively. It may suggest the need to investigate the potential interventions targeting these key pathways.

Keywords: sleep, poor sleep, unhealthy sleep behaviors, disease trajectory, UK Biobank

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468 A Rare Form of Rapidly Progressive Parkinsonism Associated with Dementia

Authors: Murat Emre, Zeynep Tufekcioglu

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Objective: We describe a patient with late onset phenylketonuria which presented with rapidly progressive dementia and parkinsonism that were reversible after management. Background: Phenylketonuria is an autosomal recessive disorder due to mutations in the phenylalanine hydroxlase gene. It normally presents in childhood, in rare cases, however, it may have its onset in adulthood and may mimic other neurological disorders. Case description: A previously normal functioning, 59 year old man was admitted for blurred vision, cognitive impairment and gait difficulty which emerged over the past eight months. In neurological examination he had brisk reflexes, slow gait and left-dominant parkinsonism. Mini-mental state examination score was 25/30, neuropsychological testing revealed a dysexecutive syndrome with constructional apraxia and simultanagnosia. In cranial MRI there were bilateral diffuse hyper-intense lesions in parietal and occipital white matter with no significant atrophy. Electroencephalography showed diffuse slowing with predominance of teta waves. In cerebrospinal fluid examination protein level was slightly elevated (61mg/dL), oligoclonal bands were negative. Electromyography was normal. Routine laboratory examinations for rapidly progressive dementia and parkinsonism were also normal. Serum amino acid levels were determined to explore metabolic leukodystrophies and phenylalanine level was found to be highly elevated (1075 µmol/L) with normal tyrosine (61,20 µmol/L). His cognitive impairment and parkinsonian symptoms improved following three months of phenylalanine restricted diet. Conclusions: Late onset phenylketonuria is a rare, potentially reversible cause of rapidly progressive parkinsonism with dementia. It should be considered in the differential diagnosis of patients with suspicious features.

Keywords: dementia, neurology, Phenylketonuria, rapidly progressive parkinsonism

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467 Macrocephaly-Cutis Marmorata Telangiectatica Congenita Associated with Epilepsy: Case Report

Authors: Atitallah Sofien, Bouyahia Olfa, Krifi Farah, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous vascular malformation. It most often appears at birth or during the first days of life. Its origin is still unknown. It associates a livedo with telangiectasias of diffuse or segmental topography. In rare cases, it can be associated with neurological disorders such as macrocephaly and, less frequently, with epilepsy. Methodology: We report a case of an infant with Macrocephaly- Cutis marmorata telangiectatica congenita syndrome associated with epilepsy. Results: This is the case of a one month and 15 days old female infant from a non-consanguineous marriage, admitted for a status epilepticus in the context of apyrexia. Infectious and metabolic causes had been eliminated. Physical examination had shown non-infiltrated and reticular livedoid erythematous patches affecting the left upper limb and atrophic on the back of the left hand. Cerebral magnetic resonance imaging (MRI) showed thin layers of bifrontal, temporal, and left parietal hygromas associated with the widening of the bifrontal subarachnoid spaces. The electroencephalogram showed a well-organized sleep tracing with a single right occipital paroxysmal abnormality. Antiepileptic treatment has been administered with good clinical evolution and regression of the skin lesion and a control electroencephalogram without abnormality. Conclusion: This observation illustrates an association of CMTC with both macrocephaly and epilepsy. This pathology, which is relatively benign and has a good prognosis, generally does not require treatment. However, a detailed examination must be carried out, and a follow-up plan must be put in place for each patient presenting with CMTC, given the risk of association with other abnormalities, which can be potentially serious.

Keywords: cutis marmorata telangiectatica congenita, macrocephaly, epilepsy, children

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466 Habitat-Specific Divergences in the Gene Repertoire among the Reference Prevotella Genomes of the Human Microbiome

Authors: Vinod Kumar Gupta, Narendrakumar M. Chaudhari, Suchismitha Iskepalli, Chitra Dutta

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Background-The community composition of the human microbiome is known to vary at distinct anatomical niches. But little is known about the nature of variations if any, at the genome/sub-genome levels of a specific microbial community across different niches. The present report aims to explore, as a case study, the variations in gene repertoire of 28 Prevotella reference draft genomes derived from different body-sites of human, as reported earlier by the Human Microbiome Consortium. Results-The analysis reveals the exclusive presence of 11798, 3673, 3348 and 934 gene families and exclusive absence of 17, 221, 115 and 645 gene families in Prevotella genomes derived from the human oral cavity, gastro-intestinal tracts (GIT), urogenital tract (UGT) and skin, respectively. The pan-genome for Prevotella remains “open”. Distribution of various functional COG categories differs appreciably among the habitat-specific genes, within Prevotella pan-genome and between the GIT-derived Bacteroides and Prevotella. The skin and GIT isolates of Prevotella are enriched in singletons involved in Signal transduction mechanisms, while the UGT and oral isolates show higher representation of the Defense mechanisms category. No niche-specific variations could be observed in the distribution of KEGG pathways. Conclusion-Prevotella may have developed distinct genetic strategies for adaptation to different anatomical habitats through selective, niche-specific acquisition and elimination of suitable gene-families. In addition, individual microorganisms tend to develop their own distinctive adaptive stratagems through large repertoires of singletons. Such in situ, habitat-driven refurbishment of the genetic makeup can impart substantial intra-lineage genome diversity within the microbes without perturbing their general taxonomic heritage.

Keywords: body niche adaptation, human microbiome, pangenome, Prevotella

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465 Association of ApoB, CETP and GALNT2 Genetic Variants with Type 2 Diabetes-Related Traits in Population from Bosnia and Herzegovina

Authors: Anida Causevic-Ramosevac, Sabina Semiz

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The aim of this study was to investigate the association of four single nucleotide polymorphisms (SNPs) - rs673548, rs693 in ApoB gene, rs1800775 in CETP gene and rs4846914 in GALNT2 gene with parameters of type 2 diabetes (T2D) and diabetic dyslipidemia in the population of Bosnia and Herzegovina (BH). Materials and methods: Our study involved 352 patients with T2D and 156 healthy subjects. Biochemical and anthropometric parameters were measured in all participants. DNA was extracted from the peripheral blood for the purpose of genetic testing. Polymorphisms in ApoB (rs673548, rs693), CETP (rs1800775) and GALNT2 (rs4846914) genes were analyzed by using Sequenom IPLEX platform. Results: Our results demonstrated significant associations for rs180075 polymorphism in CETP gene with levels of fasting insulin (p = 0.020; p = 0.027; p = 0.044), triglycerides (p = 0.046) and ALT (p = 0.031) activity in control group. In group of diabetic patients, results showed a significant association of rs673548 in ApoB gene with levels of fasting insulin (p = 0.008), HOMA-IR (p = 0.013), VLDL-C (p = 0.037) and CRP (p = 0.029) and rs693 in ApoB gene with BMI (p = 0.025), systolic blood pressure (p = 0.027), fasting insulin (p = 0.037) and HOMA-IR (p = 0.023) levels. Significant associations were also observed for rs1800775 in CETP gene with triglyceride (p = 0.023) levels and rs4846914 in GALNT2 gene with HbA1C (p = 0.013) and triglyceride (p = 0.043) levels. Conclusion: In conclusion, this is the first study that examined the impact of variations of candidate genes on a wide range of metabolic parameters in BH population. Our results suggest an association of variations of ApoB, CETP and GALNT2 genes with specific markers of T2D and dyslipidemia. Further studies would be needed in order to confirm these genetic effects in other ethnic groups as well.

Keywords: ApoB, CETP, dyslipidemia, GALNT2, type 2 diabetes

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464 Partitioning of Non-Metallic Nutrients in Lactating Crossbred Cattle Fed Buffers

Authors: Awadhesh Kishore

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The goal of the study was to determine how different non-metallic nutrients are partitioned from feed in various physiological contexts and how buffer addition in ruminant nutrition affects these processes. Six lactating crossbred dairy cows were selected and divided into three groups on the basis of their phenotypic and productive features (374±14 kg LW). Two treatments, T1 and T2, were randomly assigned to one animal from each group. Animals under T1 and T2 were moved to T2 and T1, respectively, after 30 days. T2 was the only group to receive buffers containing magnesium oxide and sodium bicarbonate at 0.0 and 0.01% of LW (the real amounts are equivalent to 75.3±4.0 and 30 7.7±2.0 g/d, respectively). T1 was used as the control. Wheat straw and berseem were part of the base diet, whereas wheat grain and mustard cake were part of the concentrate mixture. Following a 21-day feeding period, metabolic and milk production trials were carried out for seven consecutive days. The Kearl equation used the urine's calorific value to determine its volume. Chemical analyses were performed to determine the levels of nitrogen, carbohydrates, calories, and phosphorus in samples of feed, waste, buffer, mineral mixture, water, feces, urine, and milk that were collected. The information was analyzed statistically. Notable results included decreased nitrogen and carbohydrate partitioning to feces from feed, while increased calorie partitioning to milk and body storage, and increased carbohydrate partitioning to body storage. Phosphorus balance was significantly better in T2. The application of buffers in ruminant diets was found to increase the output of calories in milk, as well as the number of calories and carbohydrates stored in the body, while decreasing the amount of nitrogen in faeces. As a result, it may be advised to introduce buffers to feed crossbred dairy cattle.

Keywords: cattle, Magnesium oxide, non-metallic nutrients, partitioning, Sodium bicarbonate

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