Search results for: peripheral blood mononuclear cell (PBMC)
Commenced in January 2007
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Paper Count: 5822

Search results for: peripheral blood mononuclear cell (PBMC)

332 Doped TiO2 Thin Films Microstructural and Electrical Properties

Authors: Mantas Sriubas, Kristina Bockute, Darius Virbukas, Giedrius Laukaitis

Abstract:

In this work, the doped TiO2 (dopants – Ca, Mg) was investigated. The comparison between the physical vapour deposition methods as electron beam vapour deposition and magnetron sputtering was performed and the structural and electrical properties of the formed thin films were investigated. Thin films were deposited on different type of substrates: SiO2, Alloy 600 (Fe-Ni-Cr) and Al2O3 substrates. The structural properties were investigated using Ambios XP-200 profilometer, scanning electron microscope (SEM) Hitachi S-3400N, X-ray energy-dispersive spectroscope (EDS) Quad 5040 (Bruker AXS Microanalysis GmbH), X-ray diffractometer (XRD) D8 Discover (Bruker AXS GmbH) with glancing angles focusing geometry in a 20 – 70° range using the Cu Kα1 λ = 0.1540562 nm radiation). The impedance spectroscopy measurements were performed using Probostat® (NorECs AS) measurement cell in the frequency range from 10-1-106 Hz under reducing and oxidizing conditions in temperature range of 200 °C to 1200 °C. The investigation of the e-beam deposited Ca and Mg doped-TiO2 thin films shows that the thin films are dense without any visible pores and cavities and the thin films grow in zone T according Barna-Adamik SZM. Substrate temperature was kept 600 °C during the deposition and Ts/Tm ≈ 0.32 (substrate temperature (Ts) and coating material melting temperature (Tm)). The surface diffusion is high however, the grain boundary migration is strongly limited at this temperature. This means that structure is inhomogeneous and the columnar structure is mostly visible in the upper part of the films. According to XRD, the increasing of the Ca dopants’ concentration increases the crystallinity of the formed thin films and the crystallites size increase linearly and Ca dopants act as prohibitors. Thin films are comprised of anatase TiO2 phase with an exception of 2 % Ca doped TiO2, where a small peak of Ca arise. In the case of Mg doped-TiO2 the intensities of the XRD peaks decreases with increasing Mg molar concentration. It means that there are less diffraction planes of the particular orientation in thin films with higher impurities concentration. Thus, the crystallinity decreases with increasing Mg concentration and Mg dopants act as inhibitors. The impedance measurements show that the dopants changed the conductivity of the formed thin films. The conductivity varies from 10-3 S/cm to 10-4 S/cm at 800 °C under wet reducing conditions. The microstructure of the magnetron sputtered thin TiO2 films is different comparing to the thin films deposited using e-beam deposition therefore influencing other structural and electrical properties.

Keywords: electrical properties, electron beam deposition, magnetron sputtering, microstructure, titanium dioxide

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331 Triazenes: Unearthing Their Hidden Arsenal Against Malaria and Microbial Menace

Authors: Frans J. Smit, Wisdom A. Munzeiwa, Hermanus C. M. Vosloo, Lyn-Marie Birkholtz, Richard K. Haynes

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Malaria and antimicrobial infections remain significant global health concerns, necessitating the continuous search for novel therapeutic approaches. This abstract presents an overview of the potential use of triazenes as effective agents against malaria and various antimicrobial pathogens. Triazenes are a class of compounds characterized by a linear arrangement of three nitrogen atoms, rendering them structurally distinct from their cyclic counterparts. This study investigates the efficacy of triazenes against malaria and explores their antimicrobial activity. Preliminary results revealed significant antimalarial activity of the triazenes, as evidenced by in vitro screening against P. falciparum, the causative agent of malaria. Furthermore, the compounds exhibited broad-spectrum antimicrobial activity, indicating their potential as effective antimicrobial agents. These compounds have shown inhibitory effects on various essential enzymes and processes involved in parasite survival, replication, and transmission. The mechanism of action of triazenes against malaria involves interactions with critical molecular targets, such as enzymes involved in the parasite's metabolic pathways and proteins responsible for host cell invasion. The antimicrobial activity of the triazenes against bacteria and fungi was investigated through disc diffusion screening. The antimicrobial efficacy of triazenes has been observed against both Gram-positive and Gram-negative bacteria, as well as multidrug-resistant strains, making them potential candidates for combating drug-resistant infections. Furthermore, triazenes possess favourable physicochemical properties, such as good stability, solubility, and low toxicity, which are essential for drug development. The structural versatility of triazenes allows for the modification of their chemical composition to enhance their potency, selectivity, and pharmacokinetic properties. These modifications can be tailored to target specific pathogens, increasing the potential for personalized treatment strategies. In conclusion, this study highlights the potential of triazenes as promising candidates for the development of novel antimalarial and antimicrobial therapeutics. Further investigations are necessary to determine the structure-activity relationships and optimize the pharmacological properties of these compounds. The results warrant additional research, including MIC studies, to further explore the antimicrobial activity of the triazenes. Ultimately, these findings contribute to the development of more effective strategies for combating malaria and microbial infections.

Keywords: malaria, anti-microbials, triazene, resistance

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330 High Prevalence of Asymptomatic Dengue among Healthy Adults in Southern Malaysia: A Longitudinal Prospective Study

Authors: Nowrozy Jahan, Sharifah Syed Hassan, Daniel Reidpath

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In recent decades, Malaysia has become a dengue hyper-endemic country with the co-circulation of the four-dengue virus (DENV) serotypes. The number of symptomatic dengue cases is maintaining an increasing trend since 1995 and sharply increased in 2014. The four DENV serotypes have been co-circulating since 2000, and this pattern of cyclical dominance of sub-types contributed to the development of frequent major dengue epidemics in Malaysia. Since 2012, different Malaysian state was dominated by different serotypes. The study aims to estimate the burden of asymptomatic dengue in a healthy adult population which may act as a potential source of further symptomatic dengue infection. It also aims to identify the predominant DENV serotypes which are circulating at the community level. A longitudinal prospective community-based study was conducted in the Segamat district of Johor State, southern part of Malaysia where the number of reported dengue cases has steadily increased over the last three years (2013-2015). More specifically, the study was conducted in and around of Kampung Abdullah of Sungai Segamat sub-district which was identified as a hot spot area over the period of 2013-2015. This community-based study has been conducted by Southeast Asia Community Observatory (SEACO), an ISO-certified research platform in collaboration of the Ministry of Health Malaysia and Monash University Malaysia. It was conducted from May 2015 to May 2016. In this study, 277 apparently looking healthy respondents joined who were followed up as a cohort for four times during the one-year study period. Blood was collected to detect the serological marker of dengue at each round of follow-up. Among 277, 184 respondents (66%) joined all four rounds. Half of the study respondents were at the age-group of 45-64 years, slightly more than half of the respondents (59%) were female, and the most (69%) of them were Malay; only 35% lived in urban areas. During the baseline, the study found a very high prevalence of exposure to dengue virus; 89% of the study respondents had serological evidence of previous asymptomatic dengue infection; the majority of them did not know about it as they did not develop any symptom of dengue fever; only 13% knew as they developed symptoms. At the end of the one-year study period, 19% of respondents developed recent secondary dengue infection which was also identified by the serological marker as they did not develop any symptom (asymptomatic cases). The asymptomatic dengue incidence was higher during the rainy season compared to the dry season. All four dengue serotypes were identified in the serum of the infected respondents; among them, DENV-2 was the most prominent. Further genetic analysis is going on to identify the association of HLA-B*46 and HLA-DRB1*08 with dengue resistance. This study provides evidence for the policymakers to be aware of asymptomatic dengue infection, to develop a useful tool for raising awareness about asymptomatic dengue infection among the general population, to monitor the community participation to strengthen the individual and community level dengue prevention and control measures when neither there is vaccine nor particular treatment for dengue.

Keywords: asymptomatic, dengue, health adults, prospective study

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329 Road Map to Health: Palestinian Workers in Israel's Construction Sector

Authors: Maya de Vries Kedem, Abir Jubran, Diana Baron

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Employment in Israel offers Palestinian workers an income double what they can earn in the West Bank. The need to support their families leads many educated Palestinians to forgo finding work in their profession in the Palestinian Authority and instead look for employment in those sectors open to them in Israel, particularly the construction, agriculture, and industry sectors. The International Labor Organization estimated that about 1,200 workers in Israel die every year because of occupational diseases (diseases caused by working conditions). Construction workers in Israel are constantly exposed to dust, noise, chemical materials, and work in awkward postures, which require prolonged bending, repetitive motion, and other risk factors that can lead to illnesses and death. Occupational health is vastly neglected in Israel and construction workers are particularly at risk . As of June 2022, the Israeli quota in the construction sector for Palestinian workers stood at 80,000. Kav LaOved released a new study on the state of occupational health among Palestinian workers employed in construction in Israel. The study Roadmap to Health: Palestinian Workers in Israel's Construction Sector reviews the extent to which the health of Palestinian workers is protected at work in Israel. The report includes analysis of a survey administered to 256 workers as well as interviews with 10 workers and with 5 Israeli occupational health experts. Report highlights: • Among survey respondents, 63.9% stated that safety procedures to protect their health are rarely followed in their workplace (e.g., taking breaks, using protective gear, following restrictions on lifting heavy items, and having inspectors regularly on site to monitor safety). • All 256 Palestinian workers who participated to the survey said that their health has been directly or indirectly harmed by working in Israel and reported suffering from the following problems: orthopedic problems such as joint, hand, leg or knee problems (100%); headaches (75%); back problems (36.3%); eye problems (23.8%); breathing problems (17.6%); chronic pain (14.8%); heart problems (7.8%); and skin problems (3.5%). • Workers who are injured or do not feel well often continue working for fear of losing their payment for that day. About half of the 256 survey respondents reported that they pay brokerage fees to find an employer with a work permit, often paying between 2,000 and 3,000 NIS per month. “I have an obligation—I pay about NIS 120 a day for my permit, [and] I have to pay for it whether I work or not" a worker said. • Most Palestinian construction workers suffer from stress and mental health problems. Workers pointed to several issues that greatly affect their mood and mental state: daily crossings at crowded checkpoints where workers stand for hours; lack of sleep due to leaving home daily at 3:00-3:30 am; commuting two to four hours to work in each direction; and abusive work environments. A worker told KLO that the sight of thousands of workers standing together at the checkpoint causes “high blood pressure and the feeling that you are going to be squeezed.” Another said, “I felt that my bones would break.” In the survey workers reported suffering from insomnia (70.1%), breathing difficulties (35.8%), chest pressure (27.6%), or rapid pulse rate (12.2%).

Keywords: construction sector, palestinian workers, occupational health, Israel, occupation

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328 Other Cancers in Patients With Head and Neck Cancer

Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: Head and neck cancers (HNC) are often associated with the development of non-HNC primaries, as the risk factors that predispose patients to HNC are often risk factors for other cancers. Aim: We sought to evaluate whether there was an increased risk of smoking and alcohol-related cancers and also other cancers in HNC patients and to evaluate whether there is a difference between the rates of non-HNC primaries in Aboriginal compared with non-Aboriginal HNC patients. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single center in Western Australia, identifying 80 Aboriginal and 240 non-Aboriginal patients matched on a 1:3 ratio by sites, histology, rurality, and age. We collected data on the patient characteristics, tumour features, treatments, outcomes, and past and subsequent HNCs and non-HNC primaries. Results: In the overall study population, there were 86 patients (26.9%) with a metachronous or synchronous non-HNC primary. Non-HNC primaries were actually significantly more common in the non-Aboriginal population compared with the Aboriginal population (30% vs. 17.5%, p=0.02); however, half of these were patients with cutaneous squamous or basal cell carcinomas (cSCC/BCC) only. When cSCC/BCCs were excluded, non-Aboriginal patients had a similar rate as Aboriginal patients (16.7% vs. 15%, p=0.73). There were clearly more cSCC/BCCs in non-Aboriginal patients compared with Aboriginal patients (16.7% vs. 2.5%, p=0.001) and more patients with melanoma (2.5% vs. 0%, p value not significant (p=NS). Rates of most cancers were similar between non-Aboriginal and Aboriginal patients, including prostate (2.9% vs. 3.8%), colorectal (2.9% vs. 2.5%), kidney (1.2% vs. 1.2%), and these rates appeared comparable to Australian Age Standardised Incidence Rates (ASIR) in the general community. Oesophageal cancer occurred at double the rate in Aboriginal patients (3.8%) compared with non-Aboriginal patients (1.7%), which was far in excess of ASIRs which estimated a lifetime risk of 0.59% in the general population. Interestingly lung cancer rates did not appear to be significantly increased in our cohort, with 2.5% of Aboriginal patients and 3.3% of non-Aboriginal patients having lung cancer, which is in line with ASIRs which estimates a lifetime risk of 5% (by age 85yo). Interestingly the rate of Glioma in the non-Aboriginal population was higher than the ASIR, with 0.8% of non-Aboriginal patients developing Glioma, with Australian averages predicting a 0.6% lifetime risk in the general population. As these are small numbers, this finding may well be due to chance. Unsurprisingly, second HNCs occurred at an increased incidence in our cohort, in 12.5% of Aboriginal patients and 11.2% of non-Aboriginal patients, compared to an ASIR of 17 cases per 100,000 persons, estimating a lifetime risk of 1.70%. Conclusions: Overall, 26.9% of patients had a non-HNC primary. When cSCC/BCCs were excluded, Aboriginal and non-Aboriginal patients had similar rates of non-HNC primaries, although non-Aboriginal patients had a significantly higher rate of cSCC/BCCs. Aboriginal patients had double the rate of oesophageal primaries; however, this was not statistically significant, possibly due to small case numbers.

Keywords: head and neck cancer, synchronous and metachronous primaries, other primaries, Aboriginal

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327 Anti-Arthritic Effect of a Herbal Diet Formula Comprising Fruits of Rosa Multiflora and Flowers of Lonicera Japonica

Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu

Abstract:

Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.

Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip

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326 Acrylic Microspheres-Based Microbial Bio-Optode for Nitrite Ion Detection

Authors: Siti Nur Syazni Mohd Zuki, Tan Ling Ling, Nina Suhaity Azmi, Chong Kwok Feng, Lee Yook Heng

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Nitrite (NO2-) ion is used prevalently as a preservative in processed meat. Elevated levels of nitrite also found in edible bird’s nests (EBNs). Consumption of NO2- ion at levels above the health-based risk may cause cancer in humans. Spectrophotometric Griess test is the simplest established standard method for NO2- ion detection, however, it requires careful control of pH of each reaction step and susceptible to strong oxidants and dyeing interferences. Other traditional methods rely on the use of laboratory-scale instruments such as GC-MS, HPLC and ion chromatography, which cannot give real-time response. Therefore, it is of significant need for devices capable of measuring nitrite concentration in-situ, rapidly and without reagents, sample pretreatment or extraction step. Herein, we constructed a microspheres-based microbial optode for visual quantitation of NO2- ion. Raoutella planticola, the bacterium expressing NAD(P)H nitrite reductase (NiR) enzyme has been successfully extracted by microbial technique from EBN collected from local birdhouse. The whole cells and the lipophilic Nile Blue chromoionophore were physically absorbed on the photocurable poly(n-butyl acrylate-N-acryloxysuccinimide) [poly (nBA-NAS)] microspheres, whilst the reduced coenzyme NAD(P)H was covalently immobilized on the succinimide-functionalized acrylic microspheres to produce a reagentless biosensing system. Upon the NiR enzyme catalyzes the oxidation of NAD(P)H to NAD(P)+, NO2- ion is reduced to ammonium hydroxide, and that a colour change from blue to pink of the immobilized Nile Blue chromoionophore is perceived as a result of deprotonation reaction increasing the local pH in the microspheres membrane. The microspheres-based optosensor was optimized with a reflectance spectrophotometer at 639 nm and pH 8. The resulting microbial bio-optode membrane could quantify NO2- ion at 0.1 ppm and had a linear response up to 400 ppm. Due to the large surface area to mass ratio of the acrylic microspheres, it allows efficient solid state diffusional mass transfer of the substrate to the bio-recognition phase, and achieve the steady state response as fast as 5 min. The proposed optical microbial biosensor requires no sample pre-treatment step and possesses high stability as the whole cell biocatalyst provides protection to the enzymes from interfering substances, hence it is suitable for measurements in contaminated samples.

Keywords: acrylic microspheres, microbial bio-optode, nitrite ion, reflectometric

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325 Investigating the Antibacterial Properties and Omega-3 Levels of Evening Primrose Plant Against Multi-Drug Resistant Bacteria

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

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

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

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324 Relationship between Glycated Hemoglobin in Adolescents with Type 1 Diabetes Mellitus and Parental Anxiety and Depression

Authors: Evija Silina, Maris Taube, Maksims Zolovs

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Background: Type 1 diabetes mellitus (T1D) is the most common chronic endocrine pathology in children. The management of type 1 diabetes requires a strong diet, physical activity, lifelong insulin therapy, and proper self-monitoring of blood glucose and is usually complicated and, therefore, may result in a variety of psychosocial problems for children, adolescents, and their families. Metabolic control of the disease is determined by glycated haemoglobin (HbA1c), the main criterion for diabetes compensation. A correlation was observed between anxiety and depression levels and glycaemic control in many previous studies. It is assumed that anxiety and depression symptoms negatively affect glycaemic control. Parental psychological distress was associated with higher child self-report of stress and depressive symptoms, and it had negative effects on diabetes management. Objective: The main objective of this paper is to evaluate the relationship between parental mental health conditions (depression and anxiety) and metabolic control of their adolescents with T1DM. Methods: This cross-sectional study recruited adolescents with T1D (N=251) and their parents (N=251). The respondents completed questionnaires. The 7-item Generalized Anxiety Disorder (GAD-7) scale measured anxiety level; The Patient Health Questionnaire – 9 (PHQ-9) measured depressive symptoms. Glycaemic control of patients was assessed using the last glycated haemoglobin (HbA1c) values. GLM mediation analysis was performed to determine the potential mediating effect of the parent’s mental health conditions (depression and anxiety) on the relationship between the mental health conditions (depression and anxiety) of a child on the level of glycated hemoglobin (HbA1c). To test the significance of the mediated effect (ME) for non-normally distributed data, bootstrapping procedures (10,000 bootstrapped samples) were used. Results: 502 respondents were eligible for screening to detect anxiety and depression symptoms. Mediation analysis was performed to assess the mediating role of parent GAD-7 on the linkage between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9). The results revealed that the total effect of child GAD-7 (B = 0.479, z = 4.30, p < 0.001) on HbA1c was significant but the total effect of child PHQ-9 (B = 0.166, z = 1.49, p = 0.135) was not significant. With the inclusion of the mediating variable (parent GAD-7), the impact of child GAD-7 on HbA1c was found insignificant (B = 0.113, z=0.98, p = 0.326), the impact of child PHQ-9 on HbA1c was found also insignificant (B = 0.068, z=0.74, p = 0.458). The indirect effect of child GAD-7 on HbA1c through parent GAD-7 was found significant (B = 0.366, z = 4.31, p < 0.001) and the indirect effect of child PHQ-9 on HbA1c through parent GAD-7 was found also significant (B = 0.098, z = 2.56, p = 0.010). This indicates that the relationship between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9) is fully mediated by parent GAD-7. Conclusion: The main result suggests that glycated haemoglobin in adolescents with Type 1 diabetes is related to adolescents’ mental health via parents’ anxiety. It means that parents’ anxiety plays a more significant role in the level of glycated haemoglobin in adolescents than depression and anxiety in the adolescent.

Keywords: type 1 diabetes, adolescents, parental diabetes-specific mental health conditions, glycated haemoglobin, anxiety, depression

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323 Surface Modified Core–Shell Type Lipid–Polymer Hybrid Nanoparticles of Trans-Resveratrol, an Anticancer Agent, for Long Circulation and Improved Efficacy against MCF-7 Cells

Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

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Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

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322 Oxidative Stress Related Alteration of Mitochondrial Dynamics in Cellular Models

Authors: Orsolya Horvath, Laszlo Deres, Krisztian Eros, Katalin Ordog, Tamas Habon, Balazs Sumegi, Kalman Toth, Robert Halmosi

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Introduction: Oxidative stress induces an imbalance in mitochondrial fusion and fission processes, finally leading to cell death. The two antioxidant molecules, BGP-15 and L2286 have beneficial effects on mitochondrial functions and on cellular oxidative stress response. In this work, we studied the effects of these compounds on the processes of mitochondrial quality control. Methods: We used H9c2 cardiomyoblast and isolated neonatal rat cardiomyocytes (NRCM) for the experiments. The concentration of stressors and antioxidants was beforehand determined with MTT test. We applied 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) in 125 µM, 400 µM and 800 µM concentrations for 4 and 8 hours on H9c2 cells. H₂O₂ was applied in 150 µM and 300 µM concentration for 0.5 and 4 hours on both models. L2286 was administered in 10 µM, while BGP-15 in 50 µM doses. Cellular levels of the key proteins playing role in mitochondrial dynamics were measured in Western blot samples. For the analysis of mitochondrial network dynamics, we applied electron microscopy and immunocytochemistry. Results: Due to MNNG treatment the level of fusion proteins (OPA1, MFN2) decreased, while the level of fission protein DRP1 elevated markedly. The levels of fusion proteins OPA1 and MNF2 increased in the L2286 and BGP-15 treated groups. During the 8 hour treatment period, the level of DRP1 also increased in the treated cells (p < 0.05). In the H₂O₂ stressed cells, administration of L2286 increased the level of OPA1 in both H9c2 and NRCM models. MFN2 levels in isolated neonatal rat cardiomyocytes raised considerably due to BGP-15 treatment (p < 0.05). L2286 administration decreased the DRP1 level in H9c2 cells (p < 0.05). We observed that the H₂O₂-induced mitochondrial fragmentation could be decreased by L2286 treatment. Conclusion: Our results indicated that the PARP-inhibitor L2286 has beneficial effect on mitochondrial dynamics during oxidative stress scenario, and also in the case of directly induced DNA damage. We could make the similar conclusions in case of BGP-15 administration, which, via reducing ROS accumulation, propagates fusion processes, this way aids preserving cellular viability. Funding: GINOP-2.3.2-15-2016-00049; GINOP-2.3.2-15-2016-00048; GINOP-2.3.3-15-2016-00025; EFOP-3.6.1-16-2016-00004; ÚNKP-17-4-I-PTE-209

Keywords: H9c2, mitochondrial dynamics, neonatal rat cardiomyocytes, oxidative stress

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321 Feasibility and Acceptability of Mindfulness-Based Cognitive Therapy in People with Depression and Cardiovascular Disorders: A Feasibility Randomised Controlled Trial

Authors: Modi Alsubaie, Chris Dickens, Barnaby Dunn, Andy Gibson, Obioha Ukoumunned, Alison Evans, Rachael Vicary, Manish Gandhi, Willem Kuyken

Abstract:

Background: Depression co-occurs in 20% of people with cardiovascular disorders, can persist for years and predicts worse physical health outcomes. While psychosocial treatments have been shown to effectively treat acute depression in those with comorbid cardiovascular disorders, to date there has been no evaluation of approaches aiming to prevent relapse and treat residual depression symptoms in this group. Therefore, the current study aimed to examine the feasibility and acceptability of a randomised controlled trial design evaluating an adapted version of mindfulness-based cognitive therapy (MBCT) designed specifically for people with co-morbid depression and cardiovascular disorders. Methods: A 3-arm feasibility randomised controlled trial was conducted, comparing MBCT adapted for people with cardiovascular disorders plus treatment as usual (TAU), mindfulness-based stress reduction (MBSR) plus TAU, and TAU alone. Participants completed a set of self-report measures of depression severity, anxiety, quality of life, illness perceptions, mindfulness, self-compassion and affect and had their blood pressure taken immediately before, immediately after, and three months following the intervention. Those in the adapted-MBCT arm additionally underwent a qualitative interview to gather their views about the adapted intervention. Results: 3400 potentially eligible participants were approached when attending an outpatient appointment at a cardiology clinic or via a GP letter following a case note search. 242 (7.1%) were interested in taking part, 59 (1.7%) were screened as being suitable, and 33 (<1%) were eventually randomised to the three groups. The sample was heterogeneous in terms of whether they reported current depression or had a history of depression and the time since the onset of cardiovascular disease (one to 25 years). Of 11 participants randomised to adapted MBCT seven completed the full course, levels of home mindfulness practice were high, and positive qualitative feedback about the intervention was given. Twenty-nine out of 33 participants randomised completed all the assessment measures at all three-time points. With regards to the primary outcome (depression), five out of the seven people who completed the adapted MBCT and three out of five under MBSR showed significant clinical change, while in TAU no one showed any clinical change at the three-month follow-up. Conclusions: The adapted MBCT intervention was feasible and acceptable to participants. However, aspects of the trial design were not feasible. In particular, low recruitment rates were achieved, and there was a high withdrawal rate between screening and randomisation. Moreover, the heterogeneity in the sample was high meaning the adapted intervention was unlikely to be well tailored to all participants needs. This suggests that if the decision is made to move to a definitive trial, study recruitment procedures will need to be revised to more successfully recruit a target sample that optimally matches the adapted intervention.

Keywords: mindfulness-based cognitive therapy (MBCT), depression, cardiovascular disorders, feasibility, acceptability

Procedia PDF Downloads 194
320 Spatial Variability of Renieramycin-M Production in the Philippine Blue Sponge, Xestospongia Sp.

Authors: Geminne Manzano, Porfirio Aliño, Clairecynth Yu, Lilibeth Salvador-Reyes, Viviene Santiago

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Many marine benthic organisms produce secondary metabolites that serve as ecological roles to different biological and environmental factors. The secondary metabolites found in these organisms like algae, sponges, tunicates and worms exhibit variation at different scales. Understanding the chemical variation can be essential in deriving the evolutionary and ecological function of the secondary metabolites that may explain their patterns. Ecological surveys were performed on two collection sites representing from two Philippine marine biogeographic regions – in Oriental Mindoro located on the West Philippine Sea (WPS) and in Zamboanga del Sur located at Celebes Sea (CS), where a total of 39 Xestospongia sp. sponges were collected using SCUBA. The sponge samples were transported to the laboratory for taxonomic identification and chemical analysis. Biological and environmental factors were investigated to determine their relation to the abundance and distribution patterns and its spatial variability of their secondary metabolite production. Extracts were subjected to thin-layer chromatography and anti-proliferative assays to confirm the presence of Renieramycin-M and to test its cytotoxicity. The blue sponges were found to be more abundant on the WPS than in CS. Both the benthic community and the fish community in Oriental Mindoro, WPS and Zamboanga del Sur, CS sites are characterized by high species diversity and abundance and a very high biomass category. Environmental factors like depth and monsoonal exposure were also compared showing that wave exposure and depth are associated with the abundance and distribution of the sponges. Renieramycin-M presence using the TLC profiles between the sponge extracts from WPS and from CS showed differences in the Reniermycin-M presence and the presence of other functional groups were observed between the two sites. In terms of bioactivity, different responses were also exhibited by the sponge extracts coming from the different region. Different responses were also noted on its bioactivity depending on the cell lines tested. Exploring the influence of ecological parameters on the chemical variation can provide deeper chemical ecological insights in the knowledge and their potential varied applications at different scales. The results of this study provide further impetus in pursuing studies into patterns and processes of the chemical diversity of the Philippine blue sponge, Xestospongia sp. and the chemical ecological significance of the coral triangle.

Keywords: chemical ecology, porifera, renieramycin-m, spatial variability, Xestospongia sp.

Procedia PDF Downloads 192
319 The Relationship Between Social Support, Happiness, Work-Family Conflict and State-Trait Anxiety Among Single Mothers by Choice at Time of Covid-19 Pandemic

Authors: Shamir Balderman Orit, Shamir Michal

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Israel often deals with crisis situations, but most have been characterized as security crises (e.g., war). This is the first time that the Israel has dealt with a health and social emergency as part of a global crisis. The crisis began in January 2020 with the emergence of the novel coronavirus (Covid-19), which was defined as a pandemic (World Health Organization, 2020) and arrived in Israel in early March 2020. This study examined how single mothers by choice (SMBC) experience state anxiety (SA), social support, work–family conflict (WFC), and happiness. This group has not been studied in the context of crises in general or a global crisis. Using a snowball sample, 386 SMBCanswered an online questionnaire. The findings show a negative relationship between income and level of state anxiety. State anxiety was also negatively associated with social support, level of happiness, and WFC. Finally, a stepwise regression analysis indicated that happiness explained 34% of the variance in SA. We also found that most of the women did not turn to formal support agencies such as social workers, other Government Ministries, or municipal welfare. A positive and strong correlations was also found between SA and WFC. The findings of the study reinforce the understanding that although these women made a conscious and informed decision regarding the choice of their family cell, their situation is more complex in the absence of a spouse support. Therefore, this study, as other future studies in the field of SMBC, may contribute to the improvement of their social status and the understanding that they are a unique group. Although SMBC are a growing sector of society in the past few years, there are still special needs and special attention that is needed from the formal and informal supports systems. A comparative study of these two groups and in different countries would shed light on SA among mothers in general, regardless of their relationship status and location. Researchers should expand this study by comparing mothers in relationships and exploring how SMBC coped in other countries. In summary, the findings of the study contribute knowledge on three levels: (a) knowledge about SMBC in general and during crisis situations; (b) examination of social support using tools assessing receipt of assistance and support, some of which were developed for the present study; and (c) insights regarding counseling, accompaniment, and guidance of welfare mechanisms.

Keywords: single mothers by choice, state anxiety, social support, happiness, work-family conflict

Procedia PDF Downloads 83
318 A Seven Year Single-Centre Study of Dental Implant Survival in Head and Neck Oncology Patients

Authors: Sidra Suleman, Maliha Suleman, Stephen Brindley

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Oral rehabilitation of head and neck cancer patients plays a crucial role in the quality of life for such individuals post-treatment. Placement of dental implants or implant-retained prostheses can help restore oral function and aesthetics, which is often compromised following surgery. Conventional prosthodontic techniques can be insufficient in rehabilitating such patients due to their altered anatomy and reduced oral competence. Hence, there is a strong clinical need for the placement of dental implants. With an increasing incidence of head and neck cancer patients, the demand for such treatment is rising. Aim: The aim of the study was to determine the survival rate of dental implants in head and neck cancer patients placed at the Restorative and Maxillofacial Department, Royal Stoke University Hospital (RSUH), United Kingdom. Methodology: All patients who received dental implants between January 1, 2013 to December 31, 2020 were identified. Patients were excluded based on three criteria: 1) non-head and neck cancer patients, 2) no outpatient follow-up post-implant placement 3) provision of non-dental implants. Scanned paper notes and electronic records were extracted and analyzed. Implant survival was defined as fixtures that had remained in-situ / not required removal. Sample: Overall, 61 individuals were recruited from the 143 patients identified. The mean age was 64.9 years, with a range of 35 – 89 years. The sample included 37 (60.7%) males and 24 (39.3%) females. In total, 211 implants were placed, of which 40 (19.0%) were in the maxilla, 152 (72.0%) in the mandible and 19 (9.0%) in autogenous bone graft sites. Histologically 57 (93.4%) patients had squamous cell carcinoma, with 43 (70.5%) patients having either stage IVA or IVB disease. As part of treatment, 42 (68.9%) patients received radiotherapy, which was carried out post-operatively for 29 (69.0%) cases. Whereas 21 (34.4%) patients underwent chemotherapy, 13 (61.9%) of which were post-operative. The Median follow-up period was 21.9 months with a range from 0.9 – 91.4 months. During the study, 23 (37.7%) patients died and their data was censored beyond the date of death. Results: In total, four patients who had received radiotherapy had one implant failure each. Two mandibular implants failed secondary to osteoradionecrosis, and two maxillary implants did not survive as a result of failure to osseointegrate. The overall implant survival rates were 99.1% at three years and 98.1% at both 5 and 7 years. Conclusions: Although this data shows that implant failure rates are low, it highlights the difficulty in predicting which patients will be affected. Future studies involving larger cohorts are warranted to further analyze factors affecting outcomes.

Keywords: oncology, dental implants, survival, restorative

Procedia PDF Downloads 212
317 Biofilm Text Classifiers Developed Using Natural Language Processing and Unsupervised Learning Approach

Authors: Kanika Gupta, Ashok Kumar

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Biofilms are dense, highly hydrated cell clusters that are irreversibly attached to a substratum, to an interface or to each other, and are embedded in a self-produced gelatinous matrix composed of extracellular polymeric substances. Research in biofilm field has become very significant, as biofilm has shown high mechanical resilience and resistance to antibiotic treatment and constituted as a significant problem in both healthcare and other industry related to microorganisms. The massive information both stated and hidden in the biofilm literature are growing exponentially therefore it is not possible for researchers and practitioners to automatically extract and relate information from different written resources. So, the current work proposes and discusses the use of text mining techniques for the extraction of information from biofilm literature corpora containing 34306 documents. It is very difficult and expensive to obtain annotated material for biomedical literature as the literature is unstructured i.e. free-text. Therefore, we considered unsupervised approach, where no annotated training is necessary and using this approach we developed a system that will classify the text on the basis of growth and development, drug effects, radiation effects, classification and physiology of biofilms. For this, a two-step structure was used where the first step is to extract keywords from the biofilm literature using a metathesaurus and standard natural language processing tools like Rapid Miner_v5.3 and the second step is to discover relations between the genes extracted from the whole set of biofilm literature using pubmed.mineR_v1.0.11. We used unsupervised approach, which is the machine learning task of inferring a function to describe hidden structure from 'unlabeled' data, in the above-extracted datasets to develop classifiers using WinPython-64 bit_v3.5.4.0Qt5 and R studio_v0.99.467 packages which will automatically classify the text by using the mentioned sets. The developed classifiers were tested on a large data set of biofilm literature which showed that the unsupervised approach proposed is promising as well as suited for a semi-automatic labeling of the extracted relations. The entire information was stored in the relational database which was hosted locally on the server. The generated biofilm vocabulary and genes relations will be significant for researchers dealing with biofilm research, making their search easy and efficient as the keywords and genes could be directly mapped with the documents used for database development.

Keywords: biofilms literature, classifiers development, text mining, unsupervised learning approach, unstructured data, relational database

Procedia PDF Downloads 147
316 Comparison of Incidence and Risk Factors of Early Onset and Late Onset Preeclampsia: A Population Based Cohort Study

Authors: Sadia Munir, Diana White, Aya Albahri, Pratiwi Hastania, Eltahir Mohamed, Mahmood Khan, Fathima Mohamed, Ayat Kadhi, Haila Saleem

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Preeclampsia is a major complication of pregnancy. Prediction and management of preeclampsia is a challenge for obstetricians. To our knowledge, no major progress has been achieved in the prevention and early detection of preeclampsia. There is very little known about the clear treatment path of this disorder. Preeclampsia puts both mother and baby at risk of several short term- and long term-health problems later in life. There is huge health service cost burden in the health care system associated with preeclampsia and its complications. Preeclampsia is divided into two different types. Early onset preeclampsia develops before 34 weeks of gestation, and late onset develops at or after 34 weeks of gestation. Different genetic and environmental factors, prognosis, heritability, biochemical and clinical features are associated with early and late onset preeclampsia. Prevalence of preeclampsia greatly varies all over the world and is dependent on ethnicity of the population and geographic region. To authors best knowledge, no published data on preeclampsia exist in Qatar. In this study, we are reporting the incidence of preeclampsia in Qatar. The purpose of this study is to compare the incidence and risk factors of both early onset and late onset preeclampsia in Qatar. This retrospective longitudinal cohort study was conducted using data from the hospital record of Women’s Hospital, Hamad Medical Corporation (HMC), from May 2014-May 2016. Data collection tool, which was approved by HMC, was a researcher made extraction sheet that included information such as blood pressure during admission, socio demographic characteristics, delivery mode, and new born details. A total of 1929 patients’ files were identified by the hospital information management when they apply codes of preeclampsia. Out of 1929 files, 878 had significant gestational hypertension without proteinuria, 365 had preeclampsia, 364 had severe preeclampsia, and 188 had preexisting hypertension with superimposed proteinuria. In this study, 78% of the data was obtained by hospital electronic system (Cerner) and the remaining 22% was from patient’s paper records. We have gone through detail data extraction from 560 files. Initial data analysis has revealed that 15.02% of pregnancies were complicated with preeclampsia from May 2014-May 2016. We have analyzed difference in the two different disease entities in the ethnicity, maternal age, severity of hypertension, mode of delivery and infant birth weight. We have identified promising differences in the risk factors of early onset and late onset preeclampsia. The data from clinical findings of preeclampsia will contribute to increased knowledge about two different disease entities, their etiology, and similarities/differences. The findings of this study can also be used in predicting health challenges, improving health care system, setting up guidelines, and providing the best care for women suffering from preeclampsia.

Keywords: preeclampsia, incidence, risk factors, maternal

Procedia PDF Downloads 117
315 Effects of Tramadol Administration on the Ovary of Adult Rats and the Possible Recovery after Tramadol Withdrawal: A Light and Electron Microscopic Study

Authors: Heba Kamal Mohamed

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Introduction: Tramadol is a weak -opioid receptor agonist with an analgesic effect because of the inhibition of uptake of norepinephrine and serotonin. Nowadays, tramadol hydrochloride is frequently used as a pain reliever. Tramadol is recommended for the management of acute and chronic pain of moderate to severe intensity associated with a variety of diseases or problems, including osteoarthritis, diabetic neuropathy, neuropathic pain, and even perioperative pain in human patients. In obstetrics and gynecology, tramadol is used extensively to treat postoperative pain. Aim of the study: This study was undertaken to investigate the histological (light and electron microscopic) and immunohistochemical effects of long term tramadol treatment on the ovary of adult rats and the possible recovery after tramadol withdrawal. Design: Experimental study. Materials and methods: Thirty adult female albino rats were used in this study. They were classified into three main groups (10 rats each). Group I served as the control group. Group II, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks. Group III, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks then were kept for another 8 weeks without treatment for recovery. At the end of the experiment rats were sacrificed and bilateral oophorectomy was carried out; the ovaries were processed for histological study (light and electron microscopic) and immunohistochemical reaction for caspase-3 (apoptotic protein). Results: Examination of the ovary of tramadol-treated rats (group II) revealed many atretic ovarian follicles, some follicles showed detachment of the oocyte from surrounding granulosa cells and others showed loss of the oocyte. Many follicles revealed degenerated vacuolated oocytes and vacuolated theca folliculi cells. Granulosa cells appeared shrunken, disrupted and loosely attached with vacuolated cytoplasm and pyknotic nuclei. Some follicles showed separation of granulosa cells from the theca folliculi layer. The ultrastructural study revealed the presence of granulosa cells with electron dense indented nuclei, damaged mitochondria and granular vacuolated cytoplasm. Other cells showed accumulation of large amount of lipid droplets in their cytoplasm. Some follicles revealed rarifaction of the cytoplasm of oocytes and absent zona pellucida. Moreover, apoptotic changes were detected by immunohistochemical staining in the form of increased staining intensity to caspase-3 (apoptotic protein). With Masson's Trichrome stain, there was an increased collagen fibre deposition in the ovarian cortical stroma. The wall of blood vessels appeared thickened. In the withdrawal group (group III), there was a little improvement in the histological and immunohistochemical changes. Conclusion: Tramadol had serious deleterious effects on ovarian structure. Thus, it should be used with caution, especially when a long term treatment is indicated. Withdrawal of tramadol led to a little improvement in the structural impairment of the ovary.

Keywords: tramadol, ovary, withdrawal, rats

Procedia PDF Downloads 273
314 Microglia Activation in Animal Model of Schizophrenia

Authors: Esshili Awatef, Manitz Marie-Pierre, Eßlinger Manuela, Gerhardt Alexandra, Plümper Jennifer, Wachholz Simone, Friebe Astrid, Juckel Georg

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Maternal immune activation (MIA) resulting from maternal viral infection during pregnancy is a known risk factor for schizophrenia. The neural mechanisms by which maternal infections increase the risk for schizophrenia remain unknown, although the prevailing hypothesis argues that an activation of the maternal immune system induces changes in the maternal-fetal environment that might interact with fetal brain development. It may lead to an activation of fetal microglia inducing long-lasting functional changes of these cells. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, we hypothesize that prenatal treatment with the inflammatory agent Poly(I:C) during embryogenesis at contributes to microglial activation in the offspring, which may, therefore, represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options. Pregnant rats were treated with intraperitoneal injections a single dose of Poly(I:C) or saline on gestation day 17. Brains of control and Poly(I:C) offspring, were removed and into 20-μm-thick coronal sections were cut by using a Cryostat. Brain slices were fixed and immunostained with ba1 antibody. Subsequently, Iba1-immunoreactivity was detected using a secondary antibody, goat anti-rabbit. The sections were viewed and photographed under microscope. The immunohistochemical analysis revealed increases in microglia cell number in the prefrontal cortex, in offspring of poly(I:C) treated-rats as compared to the controls injected with NaCl. However, no significant differences were observed in microglia activation in the cerebellum among the groups. Prenatal immune challenge with Poly(I:C) was able to induce long-lasting changes in the offspring brains. This lead to a higher activation of microglia cells in the prefrontal cortex, a brain region critical for many higher brain functions, including working memory and cognitive flexibility. which might be implicated in possible changes in cortical neuropil architecture in schizophrenia. Further studies will be needed to clarify the association between microglial cells activation and schizophrenia-related behavioral alterations.

Keywords: Microglia, neuroinflammation, PolyI:C, schizophrenia

Procedia PDF Downloads 400
313 Phenotypic and Molecular Heterogeneity Linked to the Magnesium Transporter CNNM2

Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

Procedia PDF Downloads 129
312 Determination of Activation Energy for Thermal Decomposition of Selected Soft Tissues Components

Authors: M. Ekiert, T. Uhl, A. Mlyniec

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Tendons are the biological soft tissue structures composed of collagen, proteoglycan, glycoproteins, water and cells of extracellular matrix (ECM). Tendons, which primary function is to transfer force generated by the muscles to the bones causing joints movement, are exposed to many micro and macro damages. In fact, tendons and ligaments trauma are one of the most numerous injuries of human musculoskeletal system, causing for many people (particularly for athletes and physically active people), recurring disorders, chronic pain or even inability of movement. The number of tendons reconstruction and transplantation procedures is increasing every year. Therefore, studies on soft tissues storage conditions (influencing i.e. tissue aging) seem to be an extremely important issue. In this study, an atomic-scale investigation on the kinetics of decomposition of two selected tendon components – collagen type I (which forms a 60-85% of a tendon dry mass) and elastin protein (which combine with ECM creates elastic fibers of connective tissues) is presented. A molecular model of collagen and elastin was developed based on crystal structure of triple-helical collagen-like 1QSU peptide and P15502 human elastin protein, respectively. Each model employed 4 linear strands collagen/elastin strands per unit cell, distributed in 2x2 matrix arrangement, placed in simulation box filled with water molecules. A decomposition phenomena was simulated with molecular dynamics (MD) method using ReaxFF force field and periodic boundary conditions. A set of NVT-MD runs was performed for 1000K temperature range in order to obtained temperature-depended rate of production of decomposition by-products. Based on calculated reaction rates activation energies and pre-exponential factors, required to formulate Arrhenius equations describing kinetics of decomposition of tested soft tissue components, were calculated. Moreover, by adjusting a model developed for collagen, system scalability and correct implementation of the periodic boundary conditions were evaluated. An obtained results provide a deeper insight into decomposition of selected tendon components. A developed methodology may also be easily transferred to other connective tissue elements and therefore might be used for further studies on soft tissues aging.

Keywords: decomposition, molecular dynamics, soft tissue, tendons

Procedia PDF Downloads 193
311 A Second Chance to Live and Move: Lumbosacral Spinal Cord Ischemia-Infarction after Cardiac Arrest and the Artery of Adamkiewicz

Authors: Anna Demian, Levi Howard, L. Ng, Leslie Simon, Mark Dragon, A. Desai, Timothy Devlantes, W. David Freeman

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Introduction: Out-of-hospital cardiac arrest (OHCA) can carry a high mortality. For survivors, the most common complication is hypoxic-ischemic brain injury (HIBI). Rarely, lumbosacral spinal cord and/or other spinal cord artery ischemia can occur due to anatomic variation and variable mean arterial pressure after the return of spontaneous circulation. We present a case of an OHCA survivor who later woke up with bilateral leg weakness with preserved sensation (ASIA grade B, L2 level). Methods: We describe a clinical, radiographic, and laboratory presentation, as well as a National Library of Medicine (NLM) search engine methodology, characterizing incidence/prevalence of this entity is discussed. A 70-year-old male, a longtime smoker, and alcohol user, suddenly collapsed at a bar surrounded by friends. He had complained of chest pain before collapsing. 911 was called. EMS arrived, and the patient was in pulseless electrical activity (PEA), cardiopulmonary resuscitation (CPR) was initiated, and the patient was intubated, and a LUCAS device was applied for continuous, high-quality CPR in the field by EMS. In the ED, central lines were placed, and thrombolysis was administered for a suspected Pulmonary Embolism (PE). It was a prolonged code that lasted 90 minutes. The code continued with the eventual return of spontaneous circulation. The patient was placed on an epinephrine and norepinephrine drip to maintain blood pressure. ECHO was performed and showed a “D-shaped” ventricle worrisome for PE as well as an ejection fraction around 30%. A CT with PE protocol was performed and confirmed bilateral PE. Results: The patient woke up 24 hours later, following commands, and was extubated. He was found paraplegic below L2 with preserved sensation, with hypotonia and areflexia consistent with “spinal shock” or anterior spinal cord syndrome. MRI thoracic and lumbar spine showed a conus medullaris level spinal cord infarction. The patient was given IV steroids upon initial discovery of cord infarct. NLM search using “cardiac arrest” and “spinal cord infarction” revealed 57 results, with only 8 review articles. Risk factors include age, atherosclerotic disease, and intraaortic balloon pump placement. AoA (Artery of Adamkiewicz) anatomic variation along with existing atherosclerotic factors and low perfusion were also known risk factors. Conclusion: Acute paraplegia from anterior spinal cord infarction of the AoA territory after cardiac arrest is rare. Larger prospective, multicenter trials are needed to examine potential interventions of hypothermia, lumbar drains, which are sometimes used in aortic surgery to reduce ischemia and/or other neuroprotectants.

Keywords: cardiac arrest, spinal cord infarction, artery of Adamkiewicz, paraplegia

Procedia PDF Downloads 171
310 Double Liposomes Based Dual Drug Delivery System for Effective Eradication of Helicobacter pylori

Authors: Yuvraj Singh Dangi, Brajesh Kumar Tiwari, Ashok Kumar Jain, Kamta Prasad Namdeo

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The potential use of liposomes as drug carriers by i.v. injection is limited by their low stability in blood stream. Firstly, phospholipid exchange and transfer to lipoproteins, mainly HDL destabilizes and disintegrates liposomes with subsequent loss of content. To avoid the pain associated with injection and to obtain better patient compliance studies concerning various dosage forms, have been developed. Conventional liposomes (unilamellar and multilamellar) have certain drawbacks like low entrapment efficiency, stability and release of drug after single breach in external membrane, have led to the new type of liposomal systems. The challenge has been successfully met in the form of Double Liposomes (DL). DL is a recently developed type of liposome, consisting of smaller liposomes enveloped in lipid bilayers. The outer lipid layer of DL can protect inner liposomes against various enzymes, therefore DL was thought to be more effective than ordinary liposomes. This concept was also supported by in vitro release characteristics i.e. DL formation inhibited the release of drugs encapsulated in inner liposomes. DL consists of several small liposomes encapsulated in large liposomes, i.e., multivesicular vesicles (MVV), therefore, DL should be discriminated from ordinary classification of multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV). However, for these liposomes, the volume of inner phase is small and loading volume of water-soluble drugs is low. In the present study, the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore, combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Keywords: Helicobacter pylorI, amoxicillin trihydrate, Ranitidine Bismuth citrate, phosphatidylethanolamine, multi vesicular systems

Procedia PDF Downloads 181
309 Poly(ε-caprolactone)/Halloysite Nanotube Nanocomposites Scaffolds for Tissue Engineering

Authors: Z. Terzopoulou, I. Koliakou, D. Bikiaris

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Tissue engineering offers a new approach to regenerate diseased or damaged tissues such as bone. Great effort is devoted to eliminating the need of removing non-degradable implants at the end of their life span, with biodegradable polymers playing a major part. Poly(ε-caprolactone) (PCL) is one of the best candidates for this purpose due to its high permeability, good biodegradability and exceptional biocompatibility, which has stimulated extensive research into its potential application in the biomedical fields. However, PCL degrades much slower than other known biodegradable polymers and has a total degradation of 2-4 years depending on the initial molecular weight of the device. This is due to its relatively hydrophobic character and high crystallinity. Consequently, much attention has been given to the tunable degradation of PCL to meet the diverse requirements of biomedicine. Poly(ε-caprolactone) (PCL) is a biodegradable polyester that lacks bioactivity, so when used in bone tissue engineering, new bone tissue cannot bond tightly on the polymeric surface. Therefore, it is important to incorporate reinforcing fillers into PCL matrix in order to result in a promising combination of bioactivity, biodegradability, and strength. Natural clay halloysite nanotubes (HNTs) were incorporated into PCL polymeric matrix, via in situ ring-opening polymerization of caprolactone, in concentrations 0.5, 1 and 2.5 wt%. Both unmodified and modified with aminopropyltrimethoxysilane (APTES) HNTs were used in this study. The effect of nanofiller concentration and functionalization with end-amino groups on the physicochemical properties of the prepared nanocomposites was studied. Mechanical properties were found enhanced after the incorporation of nanofillers, while the modification increased further the values of tensile and impact strength. Thermal stability of PCL was not affected by the presence of nanofillers, while the crystallization rate that was studied by Differential Scanning Calorimetry (DSC) and Polarized Light Optical Microscopy (POM) increased. All materials were subjected to enzymatic hydrolysis in phosphate buffer in the presence of lipases. Due to the hydrophilic nature of HNTs, the biodegradation rate of nanocomposites was higher compared to neat PCL. In order to confirm the effect of hydrophilicity, contact angle measurements were also performed. In vitro biomineralization test confirmed that all samples were bioactive as mineral deposits were detected by X-ray diffractometry after incubation in SBF. All scaffolds were tested in relevant cell culture using osteoblast-like cells (MG-63) to demonstrate their biocompatibility

Keywords: biomaterials, nanocomposites, scaffolds, tissue engineering

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308 Mesalazine-Induced Myopericarditis in a Professional Athlete

Authors: Tristan R. Fraser, Christopher D. Steadman, Christopher J. Boos

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Myopericarditis is an inflammation syndrome characterised by clinical diagnostic criteria for pericarditis, such as chest pain, combined with evidence of myocardial involvement, such as elevation of biomarkers of myocardial damage, e.g., troponins. It can rarely be a complication of therapeutics used for dysregulated immune-mediated diseases such as inflammatory bowel disease (IBD), for example, mesalazine. The infrequency of mesalazine-induced myopericarditis adds to the challenge in its recognition. Rapid diagnosis and the early introduction of treatment are crucial. This case report follows a 24-year-old professional footballer with a past medical history of ulcerative colitis, recently started on mesalazine for disease control. Three weeks after mesalazine was initiated, he was admitted with fever, shortness of breath, and chest pain worse whilst supine and on deep inspiration, as well as elevated venous blood cardiac troponin T level (cTnT, 288ng/L; normal: <13ng/L). Myocarditis was confirmed on initial inpatient cardiac MRI, revealing the presence of florid myocarditis with preserved left ventricular systolic function and an ejection fraction of 67%. This was a longitudinal case study following the progress of a single individual with myopericarditis over four acute hospital admissions over nine weeks, with admissions ranging from two to five days. Parameters examined included clinical signs and symptoms, serum troponin, transthoracic echocardiogram, and cardiac MRI. Serial measurements of cardiac function, including cardiac MRI and transthoracic echocardiogram, showed progressive deterioration of cardiac function whilst mesalazine was continued. Prior to cessation of mesalazine, transthoracic echocardiography revealed a small global pericardial effusion of < 1cm and worsening left ventricular systolic function with an ejection fraction of 45%. After recognition of mesalazine as a potential cause and consequent cessation of the drug, symptoms resolved, with cardiac MRI performed as an outpatient showing resolution of myocardial oedema. The patient plans to make a return to competitive sport. Patients suffering from myopericarditis are advised to refrain from competitive sport for at least six months in order to reduce the risk of cardiac remodelling and sudden cardiac death. Additional considerations must be taken in individuals for whom competitive sport is an essential component of their livelihood, such as professional athletes. Myopericarditis is an uncommon, however potentially serious medical condition with a wide variety of aetiologies, including viral, autoimmune, and drug-related causes. Management is mainly supportive and relies on prompt recognition and removal of the aetiological process. Mesalazine-induced myopericarditis is a rare condition; as such increasing awareness of mesalazine as a precipitant of myopericarditis is vital for optimising the management of these patients.

Keywords: myopericarditis, mesalazine, inflammatory bowel disease, professional athlete

Procedia PDF Downloads 117
307 Moringa olifera Curate The Toxic Potential of CuO Nanoparticles in Oreochromis mossambicus

Authors: Farhat Jabeen, Muhammad Asad

Abstract:

The study assessed the curative potential of Moringa olifera seeds against copper oxide nanoparticles induced toxicity in Oreochromis mossambicus. In order to investigate the curative potential of M. olifera seeds, firstly we examine its chemical composition, secondary metabolites, and bioactive compounds including hydroxyl-cinnamic acids, flavanols and hydroxybenzoic acids through standard methods and high performance liquid chromatography. In current study, the potential sub-lethal toxic dose of CuO-NPs (0.12 mg/l) was investigated through pilot experiment and three non-lethal doses (low=32, medium=48 and high=96 mg/l) of M. olifera were selected on the basis of its LC50 value for O. mossambicus. The experimental fish, O. mossambicus (n=100 of approximately 20 g each) were procured from Manawan Fisheries Complex, Lahore, and acclimatized for two weeks in glass aquaria. Experiment was conducted in accordance with the guidelines of Institutional Animal Ethics Committee, Government College University Faisalabad, Pakistan. During acclimatization and experimental period, fish received the commercial fish feed at 2.5% body weight daily. In order to assess the curative effect of M. olifera against CuO NPs induced toxicity, O. mossambicus were randomly divided into five groups and were designated as control (C) without any treatment, positive control (G*) exposed to potential toxic dose of CuO-NPs at 0.12 mg/l, and three treated groups namely G1, G2, and G3 co-treated with 0.12 mg/l of CuO-NPs plus different doses of M. olifera seed extract at 32, 48, and 96 mg/l, respectively for 56 days. Fish were exposed to waterborne CuO NPs and M. olifera seed extract. CuO-NPs treatment was ceased after 28 days but the doses of M. olifera were continued for 56 days. Blood was taken after 28 and 56 days through caudal venipuncture. Liver and intestine were taken for oxidative stress and histological studies after 56 days. In M. olifera seeds, moisture contents, crude protein, lipids, carbohydrates and ash were recorded as 3.8, 37.83, 32.52, 46.12, and 7.75%, respectively on dry weight basis. Total energy was recorded as 627.36 kcal/100g. Qualitative analysis of M. olifera seeds showed the presence of terpenoids, saponins, flavonoids, alkaloids and phenolics, while its quantitative analysis showed the considerable amount of total phenolics, flavonoids, saponins, and alkaloids as 134.75, 170.15, 1.57, and 0.4 µg/mg, respectively. Analysis of bioactive compounds in M. olifera seeds showed the presence of hydroxy-cinnamic acids (6.07 µg/ml), flavanols (71.72 µg/ml), and hydroxyl benzoic acids (97.82 µg/ml). The results showed that M. oliefera seed extract at 48 and 56 mg/l was able to cure against the toxic effects of CuO-NPs. The significant changes were observed in G* and G1 for sero-hepatic enzymes, anti-oxidants and histological profile. The investigations of this study showed that M. olifera is a good curative agent against potential induced toxicity of CuO-NPs in O. mossambicus. The curative effect of M. olifera is attributed to the presence of higher amount of secondary metabolites and bioactive compounds. This study suggested the use of M. olifera to curate different ailments in fish and other organisms.

Keywords: CuO nanoparticles, curative, Moringa olifera, Oreochromis mossambicus

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306 Transverse Behavior of Frictional Flat Belt Driven by Tapered Pulley -Change of Transverse Force Under Driving State–

Authors: Satoko Fujiwara, Kiyotaka Obunai, Kazuya Okubo

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A skew is one of important problems for designing the conveyor and transmission with frictional flat belt, in which running belt is deviated in width direction due to the transverse force applied to the belt. The skew often not only degrades the stability of the path of belt but also causes some damages of the belt and auxiliary machines. However, the transverse behavior such as the skew has not been discussed quantitatively in detail for frictional belts. The objective of this study is to clarify the transverse behavior of frictional flat belt driven by tapered pulley. Commercially available rubber flat belt reinforced by polyamide film was prepared as the test belt where the thickness and length were 1.25 mm and 630 mm, respectively. Test belt was driven between two pulleys made of aluminum alloy, where diameter and inter-axial length were 50 mm and 150 mm, respectively. Some tapered pulleys were applied where tapered angles were 0 deg (for comparison), 2 deg, 4 deg, and 6 deg. In order to alternatively investigate the transverse behavior, the transverse force applied to the belt was measured when the skew was constrained at the string under driving state. The transverse force was measured by a load cell having free rollers contacting on the side surface of the belt when the displacement in the belt width direction was constrained. The conditions of observed bending stiffness in-plane of the belt were changed by preparing three types of belts (the width of the belt was 20, 30, and 40 mm) where their observed stiffnesses were changed. The contributions of the bending stiffness in-plane of belt and initial inter-axial force to the transverse were discussed in experiments. The inter-axial force was also changed by setting a distance (about 240 mm) between the two pulleys. Influence of observed bending stiffness in-plane of the belt and initial inter-axial force on the transverse force were investigated. The experimental results showed that the transverse force was increased with an increase of observed bending stiffness in-plane of the belt and initial inter-axial force. The transverse force acting on the belt running on the tapered pulley was classified into multiple components. Those were components of forces applied with the deflection of the inter-axial force according to the change of taper angle, the resultant force by the bending moment applied on the belt winding around the tapered pulley, and the reaction force applied due to the shearing deformation. The calculation result of the transverse force was almost agreed with experimental data when those components were formulated. It was also shown that the most contribution was specified to be the shearing deformation, regardless of the test conditions. This study found that transverse behavior of frictional flat belt driven by tapered pulley was explained by the summation of those components of forces.

Keywords: skew, frictional flat belt, transverse force, tapered pulley

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305 Glutamine Supplementation and Resistance Traning on Anthropometric Indices, Immunoglobulins, and Cortisol Levels

Authors: Alireza Barari, Saeed Shirali, Ahmad Abdi

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Introduction: Exercise has contradictory effects on the immune system. Glutamine supplementation may increase the resistance of the immune system in athletes. The Glutamine is one of the most recognized immune nutrients that as a fuel source, substrate in the synthesis of nucleotides and amino acids and is also known to be part of the antioxidant defense. Several studies have shown that improving glutamine levels in plasma and tissues can have beneficial effects on the function of immune cells such as lymphocytes and neutrophils. This study aimed to investigate the effects of resistance training and training combined with glutamine supplementation to improve the levels of cortisol and immunoglobulin in untrained young men. The research shows that physical training can increase the cytokines in the athlete’s body of course; glutamine can counteract the negative effects of resistance training on immune function and stability of the mast cell membrane. Materials and methods: This semi-experimental study was conducted on 30 male non-athletes. They were randomly divided into three groups: control (no exercise), resistance training, resistance training and glutamine supplementation, respectively. Resistance training for 4 weeks and glutamine supplementation in 0.3 gr/kg/day after practice was applied. The resistance-training program consisted of eight exercises (leg press, lat pull, chest press, squat, seatedrow, abdominal crunch, shoulder press, biceps curl and triceps press down) four times per week. Participants performed 3 sets of 10 repetitions at 60–75% 1-RM. Anthropometry indexes (weight, body mass index, and body fat percentage), oxygen uptake (VO2max) Maximal, cortisol levels of immunoglobulins (IgA, IgG, IgM) were evaluated Pre- and post-test. Results: Results showed four week resistance training with and without glutamine cause significant increase in body weight, BMI and significantly decreased (P < 0/001) in BF. Vo2max also increased in both groups of exercise (P < 0/05) and exercise with glutamine (P < 0/001), such as in both groups significant reduction in IgG (P < 0/05) was observed. But no significant difference observed in levels of cortisol, IgA, IgM in any of the groups. No significant change observed in either parameter in the control group. No significant difference observed between the groups. Discussion: The alterations in the hormonal and immunological parameters can be used in order to assess the effect overload on the body, whether acute or chronically. The plasmatic concentration of glutamine has been associated to the functionality of the immunological system in individuals sub-mitted to intense physical training. resistance training has destructive effects on the immune system and glutamine supplementation cannot neutralize the damaging effects of power exercise on the immune system.

Keywords: glutamine, resistance traning, immuglobulins, cortisol

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304 Clinical and Analytical Performance of Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase L1 Biomarkers for Traumatic Brain Injury in the Alinity Traumatic Brain Injury Test

Authors: Raj Chandran, Saul Datwyler, Jaime Marino, Daniel West, Karla Grasso, Adam Buss, Hina Syed, Zina Al Sahouri, Jennifer Yen, Krista Caudle, Beth McQuiston

Abstract:

The Alinity i TBI test is Therapeutic Goods Administration (TGA) registered and is a panel of in vitro diagnostic chemiluminescent microparticle immunoassays for the measurement of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) in plasma and serum. The Alinity i TBI performance was evaluated in a multi-center pivotal study to demonstrate the capability to assist in determining the need for a CT scan of the head in adult subjects (age 18+) presenting with suspected mild TBI (traumatic brain injury) with a Glasgow Coma Scale score of 13 to 15. TBI has been recognized as an important cause of death and disability and is a growing public health problem. An estimated 69 million people globally experience a TBI annually1. Blood-based biomarkers such as glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have shown utility to predict acute traumatic intracranial injury on head CT scans after TBI. A pivotal study using prospectively collected archived (frozen) plasma specimens was conducted to establish the clinical performance of the TBI test on the Alinity i system. The specimens were originally collected in a prospective, multi-center clinical study. Testing of the specimens was performed at three clinical sites in the United States. Performance characteristics such as detection limits, imprecision, linearity, measuring interval, expected values, and interferences were established following Clinical and Laboratory Standards Institute (CLSI) guidance. Of the 1899 mild TBI subjects, 120 had positive head CT scan results; 116 of the 120 specimens had a positive TBI interpretation (Sensitivity 96.7%; 95% CI: 91.7%, 98.7%). Of the 1779 subjects with negative CT scan results, 713 had a negative TBI interpretation (Specificity 40.1%; 95% CI: 37.8, 42.4). The negative predictive value (NPV) of the test was 99.4% (713/717, 95% CI: 98.6%, 99.8%). The analytical measuring interval (AMI) extends from the limit of quantitation (LoQ) to the upper LoQ and is determined by the range that demonstrates acceptable performance for linearity, imprecision, and bias. The AMI is 6.1 to 42,000 pg/mL for GFAP and 26.3 to 25,000 pg/mL for UCH-L1. Overall, within-laboratory imprecision (20 day) ranged from 3.7 to 5.9% CV for GFAP and 3.0 to 6.0% CV for UCH-L1, when including lot and instrument variances. The Alinity i TBI clinical performance results demonstrated high sensitivity and high NPV, supporting the utility to assist in determining the need for a head CT scan in subjects presenting to the emergency department with suspected mild TBI. The GFAP and UCH-L1 assays show robust analytical performance across a broad concentration range of GFAP and UCH-L1 and may serve as a valuable tool to help evaluate TBI patients across the spectrum of mild to severe injury.

Keywords: biomarker, diagnostic, neurology, TBI

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303 Metal Contents in Bird Feathers (Columba livia) from Mt Etna Volcano: Volcanic Plume Contribution and Biological Fractionation

Authors: Edda E. Falcone, Cinzia Federico, Sergio Bellomo, Lorenzo Brusca, Manfredi Longo, Walter D’Alessandro

Abstract:

Although trace metals are an essential element for living beings, they can become toxic at high concentrations. Their potential toxicity is related not only to the total content in the environment but mostly upon their bioavailability. Volcanoes are important natural metal emitters and they can deeply affect the quality of air, water and soils, as well as the human health. Trace metals tend to accumulate in the tissues of living organisms, depending on the metal contents in food, air and water and on the exposure time. Birds are considered as bioindicators of interest, because their feathers directly reflects the metals uptake from the blood. Birds are exposed to the atmospheric pollution through the contact with rainfall, dust, and aerosol, and they accumulate metals over the whole life cycle. We report on the first data combining the rainfall metal content in three different areas of Mt Etna, variably fumigated by the volcanic plume, and the metal contents in the feathers of pigeons, collected in the same areas. Rainfall samples were collected from three rain gauges placed at different elevation on the Eastern flank of the volcano, the most exposed to airborne plume, filtered, treated with HNO₃ Suprapur-grade and analyzed for Fe, Cr, Co, Ni, Se, Zn, Cu, Sr, Ba, Cd and As by ICP-MS technique, and major ions by ion chromatography. Feathers were collected from single individuals, in the same areas where the rain gauges were installed. Additionally, some samples were collected in an urban area, poorly interested by the volcanic plume. The samples were rinsed in MilliQ water and acetone, dried at 50°C until constant weight and digested in a mixture of 2:1 HNO₃ (65%) - H₂O₂ (30%) Suprapur-grade for 25-50 mg of sample, in a bath at near-to-boiling temperature. The solutions were diluted up to 20 ml prior to be analyzed by ICP-MS. The rainfall samples most contaminated by the plume were collected at close distance from the summit craters (less than 6 km), and show lower pH values and higher concentrations for all analyzed metals relative to those from the sites at lower elevation. Analyzed samples are enriched in both metals directly emitted by the volcanic plume and transported by acidic gases (SO₂, HCl, HF), and metals leached from the airborne volcanic ash. Feathers show different patterns in the different sites related to the exposure to natural or anthropogenic pollutants. They show abundance ratios similar to rainfall for lithophile elements (Ba, Sr), whereas are enriched in Zn and Se, known for their antioxidant properties, probably as adaptive response to oxidative stress induced by toxic metal exposure. The pigeons revealed a clear heterogeneity of metal uptake in the different parts of the volcano, as an effect of volcanic plume impact. Additionally, some physiological processes can modify the fate of some metals after uptake and this offer some insights for translational studies.

Keywords: bioindicators, environmental pollution, feathers, trace metals, volcanic plume

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