Search results for: silent disease
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3798

Search results for: silent disease

1278 The Impact of Covid-19 Pandemic on Acute Urology Admissions in a Busy District General Hospital in the UK

Authors: D. Bheenick, M. Young, M.Elmussareh, A.Ali

Abstract:

Objective: Coronavirus disease 2019 (COVID-19) has had unprecedented effects on the healthcare system in the UK. The pandemic has impacted every service within secondary care, including urology. Our objective is to determine how COVID-19 has influenced acute urology admissions in a busy district general hospital in the UK. Patient and methods: Retrospective data of patients presenting acutely to the urology department was collected between 13th January to 22nd March 2020 (pre-lockdown period) and 23rd March to 31st May 2020 (lockdown period). The nature of referrals, types of admission encountered, and management required in accordance with the new set of protocols established during the lockdown period were analysed and compared to the same data prior to UK lockdown. Results: 1092 patients were included in the study. An overall reduction of 32.5% was seen in the total number of admissions. A marked decrease was seen in non-urological pathology as compared to other categories. Urolithiasis showed the highest proportional increase. Treatment varied proportionately to the diagnosis, with conservative management accounting for the most likely treatment during lockdown. However, the proportion of patients requiring interventions during the lockdown period increased overall. No comparative differences were observed during the two periods in terms of source of referral, length of stay and patient age. Conclusion: The admission rate showed a decrease, with no significant difference in the nature and timing of presentation. Our department was able to continue providing effective management to patients presenting acutely during the COVID-19 outbreak.

Keywords: COVID-19, lockdown, admissions, urology

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1277 Advances in Sesame Molecular Breeding: A Comprehensive Review

Authors: Micheale Yifter Weldemichael

Abstract:

Sesame (Sesamum indicum L.) is among the most important oilseed crops for its high edible oil quality and quantity. Sesame is grown for food, medicinal, pharmaceutical, and industrial uses. Sesame is also cultivated as a main cash crop in Asia and Africa by smallholder farmers. Despite the global exponential increase in sesame cultivation area, its production and productivity remain low, mainly due to biotic and abiotic constraints. Notwithstanding the efforts to solve these problems, a low level of genetic variation and inadequate genomic resources hinder the progress of sesame improvement. The objective of this paper is, therefore, to review recent advances in the area of molecular breeding and transformation to overcome major production constraints and could result in enhanced and sustained sesame production. This paper reviews various researches conducted to date on molecular breeding and genetic transformation in sesame focusing on molecular markers used in assessing the available online database resources, genes responsible for key agronomic traits as well as transgenic technology and genome editing. The review concentrates on quantitative and semi-quantitative studies on molecular breeding for key agronomic traits such as improvement of yield components, oil and oil-related traits, disease and insect/pest resistance, and drought, waterlogging and salt tolerance, as well as sesame genetic transformation and genome editing techniques. Pitfalls and limitations of existing studies and methodologies used so far are identified and some priorities for future research directions in sesame genetic improvement are identified in this review.

Keywords: abiotic stress, biotic stress, improvement, molecular breeding, oil, sesame, shattering

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1276 Surveillance of Hepatitis C Virus Genotype Circulating in North India

Authors: Shantanu Prakash, Suruchi Shukla, Amita Jain

Abstract:

Introduction: The hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease. Injection drug use and individuals receiving blood and blood products are the primary modes of HCV transmission. Our study aims to establish the prevalent genotypes/ subtypes of HCV circulating in Uttar Pradesh, North India, as reported from a tertiary care hospital. Methods: It is a retrospective observational analysis of consecutive 404 HCV RNA positive cases referred to our hospital during September 2014 to April 2017. The study was approved by an institutional ethics committee. Written informed consent was taken from each participant. Clinical and demographic details of these patients were recorded using predesigned questionnaires. All the laboratory testing was carried on stored serum sample of enrolled cases. Genotyping of all 404 strains was done by Sanger’s sequencing of the core region. The phylogenetic analysis of 179 HCV strains with high -quality sequencing data was performed. Results: The distribution of prevalent genotypes/ subtypes as noted in the present study was; Genotype (GT)1a [n-101(25%)], GT1b [n-12(2.9%)], GT1c [1(0.25%)], GT3a [275(68.07%)], GT3b [9(2.2%)], GT3g [2(0.49%)], GT3i [3(0.74%)], and GT4a [1(0.24%)]. HCV genotypes GT2, GT5 and GT6 were not detected from our region. Sequence analysis showed high genotypic variability in HCV GT3. Phylogenetic analysis showed that HCV GT3 and GT1 circulating in our region were related to Indian strains reported earlier. Conclusions: HCV genotypes 3a and 1a are commonest circulating genotypes in Uttar Pradesh (UP), India.

Keywords: Hepatitis C virus, genetic variation, bioinformatics, genotype, HCV

Procedia PDF Downloads 138
1275 The Impact of Social Interaction, Wellbeing and Mental Health on Student Achievement During COVID-19 Lockdown in Saudi Arabia

Authors: Shatha Ahmad Alharthi

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Prior research suggests that reduced social interaction can negatively affect well-being and impair mental health (e.g., depression and anxiety), resulting in lower academic performance. The COVID-19 pandemic has significantly limited social interaction among Saudi Arabian school children since the government closed schools and implemented lockdown restrictions to reduce the spread of the disease. These restrictions have resulted in prolonged remote learning for middle school students with unknown consequences for perceived academic performance, mental health, and well-being. This research project explores how middle school Saudi students’ current remote learning practices affect their mental health (e.g., depression and anxiety) and well-being during the lockdown. Furthermore, the study will examine the association between social interaction, mental health, and well-being pertaining to students’ perceptions of their academic achievement. Research findings could lead to a better understanding of the role of lockdown on depression, anxiety, well-being and perceived academic performance. Research findings may also inform policy-makers or practitioners (e.g., teachers and school leaders) about the importance of facilitating increased social interactions in remote learning situations and help to identify important factors to consider when seeking to re-integrate students into a face-to-face classroom setting. Potential implications for future educational research include exploring remote learning interventions targeted at bolstering students’ mental health and academic achievement during periods of remote learning.

Keywords: depression, anxiety, academic performance, social interaction

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1274 Hyaluronan and Hyaluronan-Associated Genes in Human CD8 T Cells

Authors: Emily Schlebes, Christian Hundhausen, Jens W. Fischer

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The glycosaminoglycan hyaluronan (HA) is a major component of the extracellular matrix, typically produced by fibroblasts of the connective tissue but also by immune cells. Here, we investigated the capacity of human peripheral blood CD8 T cells from healthy donors to produce HA and to express HA receptors as well as HA degrading enzymes. Further, we evaluated the effect of pharmacological HA inhibition on CD8 T cell function. Using immunocytochemistry together with quantitative PCR analysis, we found that HA synthesis is rapidly induced upon antibody-induced T cell receptor (TCR) activation and almost exclusively mediated by HA synthase 3 (HAS3). TCR activation also resulted in the upregulation of HA receptors CD44, hyaluronan-mediated motility receptor (HMMR), and layilin (LAYN), although kinetics and strength of expression varied greatly between subjects. The HA-degrading enzymes HYAL1 and HYAL2 were detected at low levels and induced by cell activation in some individuals. Interestingly, expression of HAS3, HA receptors, and hyaluronidases were modulated by the proinflammatory cytokines IL-6 and IL-1bβ in most subjects. To assess the functional role of HA in CD8 T cells, we performed carboxyfluorescein succinimidyl ester (CFSE) based proliferation assays and cytokine analysis in the presence of the HA inhibitor 4- Methylumbelliferone (4-MU). Despite significant inter-individual variation with regard to the effective dose, 4-MU resulted in the inhibition of CD8 T cell proliferation and reduced release of TNF-α and IFN-γ. Collectively, these data demonstrate that human CD8 T cells respond to TCR stimulation with a synthesis of HA and expression of HA-related genes. They further suggest that HA inhibition may be helpful in interfering with pathogenic T cell activation in human disease.

Keywords: CD8 T cells, extracellular matrix, hyaluronan, hyaluronan synthase 3

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1273 Clinical Signs of Neonatal Calves in Experimental Colisepticemia

Authors: Samad Lotfollahzadeh

Abstract:

Escherichia coli (E.coli) is the most isolated bacteria from blood circulation of septicemic calves. Given the prevalence of septicemia in animals and its economic importance in veterinary practice, better understanding of changes in clinical signs following disease, may contribute to early detection of the disorder. The present study has been carried out to detect changes of clinical signs in induced sepsis in calves with E.coli. Colisepticemia has been induced in 10 twenty-day old healthy Holstein- Frisian calves with intravenous injection of 1.5 X 109 colony forming units (cfu) of O111: H8 strain of E.coli. Clinical signs including rectal temperature, heart rate, respiratory rate, shock, appetite, sucking reflex, feces consistency, general behavior, dehydration and standing ability were recorded in experimental calves during 24 hours after induction of colisepticemia. Blood culture was also carried out from calves four times during the experiment. ANOVA with repeated measure is used to see changes of calves’ clinical signs to experimental colisepticemia, and values of P≤ 0.05 was considered statistically significant. Mean values of rectal temperature and heart rate as well as median values of respiratory rate, appetite, suckling reflex, standing ability and feces consistency of experimental calves increased significantly during the study (P<0.05). In the present study, median value of shock score was not significantly increased in experimental calves (P> 0.05). The results of present study showed that total score of clinical signs in calves with experimental colisepticemia increased significantly, although the score of some clinical signs such as shock did not change significantly.

Keywords: calves, clinical signs scoring, E. coli O111:H8, experimental colisepticemia

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1272 Preparation of Frozen Bivalent Babesial (Babesia Bovis and Babesia Bigemina) Vaccine from Field Isolates and Evaluation of Its Efficacy in Calves

Authors: Muhammad Fiaz Qamar, Ahmad Faraz, Muhammad Arfan Zaman, Kazim Ali, Waleed Akram

Abstract:

Babesiosis is reflected as the most important disease of cattle that are transmitted by arthropods. In Pakistan, its prevalence is up to 29% in the cattle and buffalo population in different regions. Cattle show a long lasting and durable immunity by giving an infection of B.bovis, B. bigemina, or Babesiadivergens. this is used in cattle to immunize them in a few countries as anti-babesiosis vaccine. Development of frozen vaccine allows for complete testing after production of each batch, However, once thawed, its reduced its shelf life, frozen vaccines are more difficult to transport as well as expensive to produce as compared to chilled vaccine. The contamination of blood derived vaccine has the potential risk that makes pre-production and post-production quality control necessary. For the trail master seed production of whole blood frozen bivalent Babesia(Babesiabovis and Babesiabigemina), 100 blood samples of Babesial positive suspected cattle was taken and processed for separation microscopic detection and rectification by PCR. Vaccine passages were done to reduce the parasitaemiasis in live calves. After 8 passages, parasitemia of Babesia reduced from 80% to 15%. Infected donor calf’s blood was taken by jugular cannulation by using preservative free lithium heparin as an anticoagulant (5 International Units IU heparin/ml blood). In lab, parasite containing blood was mixed in equal volumes with 3 M glycerol in PBS supplemented with 5 mM glucose (final concentration of glycerol 1.5 M) at 37°C. The mixture was then equilibrized at 37°C for 30 minutes and were dispensed in required containers (e.g., 5 ml cryovials).

Keywords: distribution, babesia, primer sequences, PCV

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1271 Examining Resilience, Social Supports, and Self-Esteem as Predictors of the Quality of Life of ODAPUS (Orang Dengan Lupus)

Authors: Yulmaida Amir, Fahrul Rozi, Insany C. Kamil, Fanny Aryani

Abstract:

ODAPUS (Orang dengan Lupus) is an Indonesian term for people with Lupus, a chronic autoimmune disease in which immune system of the body becomes hyperactive and attacks normal tissue. The number of ODAPUS indicate an increase in Indonesia, thereby helping to improve their quality of life to be important to help their recovery. This study aims to examine the effect of resilience, self-esteem, and social support on the quality of life of women who had been diagnosed as having Lupus. Data were collected from 64 ODAPUS in Indonesia, using the World Health Organization Quality of Life (WHOQOL), Resilience Scale from Wagnil and Young (1993), self-esteem scale (developed from Coopersmith’s theory), and Social Support Questioner from Northouse (1988). Regression data analysis showed that resilience, social support, and self-esteem predict the quality of life of the ODAPUS simultaneously. If the variable was analysed individually, self-esteem did not significantly contribute to the quality of life. Resilience contributed most significantly to the quality of life, followed by social support. Of five sources of social supports included in the research, support from family members (parents and brother/sisters) has the most significant contribution to the quality of life, followed by support from spouse, and from friends. Interestingly, social support from medical personnel (medical doctors and nurses) had not a significant contribution to the quality of life of ODAPUS. As a conclusion, this research showed that the ability of ODAPUS to cope with difficulty in life, and support from family members, spouse, and friends were the significant predictors for their quality of life.

Keywords: quality of life, resilience, self-esteem, social supports

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1270 Advanced Magnetic Resonance Imaging in Differentiation of Neurocysticercosis and Tuberculoma

Authors: Rajendra N. Ghosh, Paramjeet Singh, Niranjan Khandelwal, Sameer Vyas, Pratibha Singhi, Naveen Sankhyan

Abstract:

Background: Tuberculoma and neurocysticercosis (NCC) are two most common intracranial infections in developing country. They often simulate on neuroimaging and in absence of typical imaging features cause significant diagnostic dilemmas. Differentiation is extremely important to avoid empirical exposure to antitubercular medications or nonspecific treatment causing disease progression. Purpose: Better characterization and differentiation of CNS tuberculoma and NCC by using morphological and multiple advanced functional MRI. Material and Methods: Total fifty untreated patients (20 tuberculoma and 30 NCC) were evaluated by using conventional and advanced sequences like CISS, SWI, DWI, DTI, Magnetization transfer (MT), T2Relaxometry (T2R), Perfusion and Spectroscopy. rCBV,ADC,FA,T2R,MTR values and metabolite ratios were calculated from lesion and normal parenchyma. Diagnosis was confirmed by typical biochemical, histopathological and imaging features. Results: CISS was most useful sequence for scolex detection (90% on CISS vs 73% on routine sequences). SWI showed higher scolex detection ability. Mean values of ADC, FA,T2R from core and rCBV from wall of lesion were significantly different in tuberculoma and NCC (P < 0.05). Mean values of rCBV, ADC, T2R and FA for tuberculoma and NCC were (3.36 vs1.3), (1.09x10⁻³vs 1.4x10⁻³), (0.13 x10⁻³ vs 0.09 x10⁻³) and (88.65 ms vs 272.3 ms) respectively. Tuberculomas showed high lipid peak, more choline and lower creatinine with Ch/Cr ratio > 1. T2R value was most significant parameter for differentiation. Cut off values for each significant parameters have proposed. Conclusion: Quantitative MRI in combination with conventional sequences can better characterize and differentiate similar appearing tuberculoma and NCC and may be incorporated in routine protocol which may avoid brain biopsy and empirical therapy.

Keywords: advanced functional MRI, differentiation, neurcysticercosis, tuberculoma

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1269 Level of IGF-I and IGFBP-3 in Gingival Crevicular Fluid and Plasma in Patients with Aggressive Periodontitis

Authors: Youjeong Hwang

Abstract:

Purpose: Insulin-like growth factor-I (IGF-I) promotes B-cell development, immunoglobulin formation, and interleukin-6 (IL-6) production, then regulate the immune response and inflammation. As IGF-I and their receptor also exist in the periodontal tissue, they may affect the immune response caused by periodontal pathogens in aggressive periodontitis (AgP) patients. The function of IGF is regulated by IGF binding proteins (IGFBPs), and IGFBP-3 is known to most abundant in plasma. The aim of the present study was to assess the concentration of IGF-I and IGFBP-3 in plasma and gingival crevicular fluid (GCF) in AgP patients and to find out their association. Methods: Nine patients with AgP (test group) and nine healthy subjects (control group) were included in this study. None of the subjects had a history of systemic disease, smoking or steroids medication. GCF samples were collected by microcapillary pipettes and plasma samples were obtained by venipuncture. Probing pocket depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were recorded. Samples were assayed for IGF-I and IGFBP-3 levels using ELISA. Results: Mean IGF-I level in GCF was higher in the test group than control. Mean IGF-I level in plasma and IGFBP-3 level in GCF and plasma in control group were higher than that of the test group. However, there was no statistical significance (p > 0.05). The mean level of IGF-I and IGFBP-3 in GCF was lower than those in plasma. Mean IGF-I level in plasma showed a negative correlation with PD and CAL (p < 0.05) in both groups. The levels of IGF-I and IGFBP-3 in GCF seemed to be negatively correlated with BOP in the test group (p < 0.05). Conclusions: The difference in the level of IGF-I and IGFBP-3 between AgP and healthy subjects was not significant. Further studies that explain the mechanism of the protective role of IGF-I with more samples are needed.

Keywords: aggressive periodontitis, pathogenesis, insulin-like growth factor, insulin-like growth factor binding protein

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1268 Black-Legged Tick (Ixodes Scapularis) Impacts on Hematology and Ectoparasite Communities of Peromyscus Mice

Authors: Erica Fellin, Albrecht Schulte-Hostedde

Abstract:

As the climate warms, the black-legged tick’s (Ixodes scapularis) range expands further north in Ontario, Canada, reaching new host populations that have not previously interacted with this blood-feeding parasite. Peromyscus mice in these northern areas are unfamiliar and inexperienced to the effects of these ticks compared to their southern counterparts that have adapted to living with these organisms. The purpose of this study was to see if there is a difference in physiology between these two groups – deer mice living in areas where tick populations have established and deer mice living in black-legged tick-free environments – looking specifically to see if there is significant variation in hemoglobin levels, which can negatively impact how these mice function in their environment. Along with this, a comparison of the parasite community structure on these mice hosts was analyzed to see if ticks change the composition of these micro-environments. Blood samples were collected from individual mice from populations where black-legged ticks were either present or absent to assess haemoglobin levels. At the same time, ectoparasites were collected from these same mice to determine parasite loads and species diversity. Haemoglobin levels were found to be lower when tick loads were high, and parasite diversity appeared to be higher when ticks were absent. Since black-legged ticks are carriers of many pathogens that can be passed on to humans, including Lyme’s disease, it is important to understand their movement and distribution across Ontario as well as their interactions with their hosts (and co-occurring parasites) in their environments.

Keywords: community ecology, hematology, hosts, parasites

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1267 Using Machine Learning to Build a Real-Time COVID-19 Mask Safety Monitor

Authors: Yash Jain

Abstract:

The US Center for Disease Control has recommended wearing masks to slow the spread of the virus. The research uses a video feed from a camera to conduct real-time classifications of whether or not a human is correctly wearing a mask, incorrectly wearing a mask, or not wearing a mask at all. Utilizing two distinct datasets from the open-source website Kaggle, a mask detection network had been trained. The first dataset that was used to train the model was titled 'Face Mask Detection' on Kaggle, where the dataset was retrieved from and the second dataset was titled 'Face Mask Dataset, which provided the data in a (YOLO Format)' so that the TinyYoloV3 model could be trained. Based on the data from Kaggle, two machine learning models were implemented and trained: a Tiny YoloV3 Real-time model and a two-stage neural network classifier. The two-stage neural network classifier had a first step of identifying distinct faces within the image, and the second step was a classifier to detect the state of the mask on the face and whether it was worn correctly, incorrectly, or no mask at all. The TinyYoloV3 was used for the live feed as well as for a comparison standpoint against the previous two-stage classifier and was trained using the darknet neural network framework. The two-stage classifier attained a mean average precision (MAP) of 80%, while the model trained using TinyYoloV3 real-time detection had a mean average precision (MAP) of 59%. Overall, both models were able to correctly classify stages/scenarios of no mask, mask, and incorrectly worn masks.

Keywords: datasets, classifier, mask-detection, real-time, TinyYoloV3, two-stage neural network classifier

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1266 Effect of Aerobic Training on Visfatin Levels and Lipid Profile in Obese Women

Authors: Banaeifar Abdolali, Rahmanimoghadam Neda, Sohyli Shahram

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Obesity is an increase in body fat , in addition it has been introduced as a risk factor for the progress of lipid disorders, hypertension, cardiovascular disease and type 2 diabetes (1,2). In recent years, Adipose tissue is now recognized as an endocrine organ that secretes many cytokines such as: interleukin 6, leptin, and visfatin (3). Visfatin is an adipocytokine that release from adiposities. It is unidentified whether training also influences concentrations of visfatin. Purpose: The purpose of this study was to examine the effects of 12 weeks of aerobic training on visfatin levels and lipid profile in obese women. Method: Thirty two obese women (age = 37.8 ± 13.2 years, body mass index = of 39.4 ± 6.4 kg/m2 .) volunteered to participate in a 12-wk exercise program. They were randomly assigned to either a training (n = 16) or control (n = 14) group. The training group exercised for 70 minutes per session, 3 days per week during the 12 week training program. The control group was asked to maintain their normal daily activities. Samples were obtained before and at the end of training program. We use t.paire and independent,test for data analyzes. Results: Exercise training resulted in a decrease in body weight (p < 0.05), percent body fat (% fat) and BMI (p < 0.05), fasting glucose level and visfatin concentration decreased but wasn’t significant (p > 0.05). Also the levels of triglyceride, total cholesterol and low-density lipoprotein cholesterol did not change significantly. Conclution: In conclusion, three month aerobic training program used in this study was very effective for producing significant benefits to body composition and HDL.c but didn’t significant chenging visfatin levels and lipid profile in these obese women.

Keywords: aerobic training, visfatin, lipid profile, women

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1265 Effect of L-Dopa on Performance and Carcass Characteristics in Broiler Chickens

Authors: B. R. O. Omidiwura, A. F. Agboola, E. A. Iyayi

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Pure form of L-Dopa is used to enhance muscular development, fat breakdown and suppress Parkinson disease in humans. However, the L-Dopa in mucuna seed, when present with other antinutritional factors, causes nutritional disorders in monogastric animals. Information on the utilisation of pure L-Dopa in monogastric animals is scanty. Therefore, effect of L-Dopa on growth performance and carcass characteristics in broiler chickens was investigated. Two hundred and forty one-day-old chicks were allotted to six treatments, which consisted of a positive control (PC) with standard energy (3100Kcal/Kg) and negative control (NC) with high energy (3500Kcal/Kg). The rest 4 diets were NC+0.1, NC+0.2, NC+0.3 and NC+0.4% L-Dopa, respectively. All treatments had 4 replicates in a completely randomized design. Body weight gain, final weight, feed intake, dressed weight and carcass characteristics were determined. Body weight gain and final weight of birds fed PC were 1791.0 and 1830.0g, NC+0.1% L-Dopa were 1827.7 and 1866.7g and NC+0.2% L-Dopa were 1871.9 and 1910.9g respectively, and the feed intake of PC (3231.5g), were better than other treatments. The dressed weight at 1375.0g and 1357.1g of birds fed NC+0.1% and NC+0.2% L-Dopa, respectively, were similar but better than other treatments. Also, the thigh (202.5g and 194.9g) and the breast meat (413.8g and 410.8g) of birds fed NC+0.1% and NC+0.2% L-Dopa, respectively, were similar but better than birds fed other treatments. The drum stick of birds fed NC+0.1% L-Dopa (220.5g) was observed to be better than birds on other diets. Meat to bone ratio and relative organ weights were not affected across treatments. L-Dopa extract, at levels tested, had no detrimental effect on broilers, rather better bird performance and carcass characteristics were observed especially at 0.1% and 0.2% L-Dopa inclusion rates. Therefore, 0.2% inclusion is recommended in diets of broiler chickens for improved performance and carcass characteristics.

Keywords: broilers, carcass characteristics, l-dopa, performance

Procedia PDF Downloads 294
1264 Evaluation of Firearm Injury Syndromic Surveillance in Utah

Authors: E. Bennion, A. Acharya, S. Barnes, D. Ferrell, S. Luckett-Cole, G. Mower, J. Nelson, Y. Nguyen

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Objective: This study aimed to evaluate the validity of a firearm injury query in the Early Notification of Community-based Epidemics syndromic surveillance system. Syndromic surveillance data are used at the Utah Department of Health for early detection of and rapid response to unusually high rates of violence and injury, among other health outcomes. The query of interest was defined by the Centers for Disease Control and Prevention and used chief complaint and discharge diagnosis codes to capture initial emergency department encounters for firearm injury of all intents. Design: Two epidemiologists manually reviewed electronic health records of emergency department visits captured by the query from April-May 2020, compared results, and sent conflicting determinations to two arbiters. Results: Of the 85 unique records captured, 67 were deemed probable, 19 were ruled out, and two were undetermined, resulting in a positive predictive value of 75.3%. Common reasons for false positives included non-initial encounters and misleading keywords. Conclusion: Improving the validity of syndromic surveillance data would better inform outbreak response decisions made by state and local health departments. The firearm injury definition could be refined to exclude non-initial encounters by negating words such as “last month,” “last week,” and “aftercare”; and to exclude non-firearm injury by negating words such as “pellet gun,” “air gun,” “nail gun,” “bullet bike,” and “exit wound” when a firearm is not mentioned.

Keywords: evaluation, health information system, firearm injury, syndromic surveillance

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1263 Retrospective Study of Positive Blood Cultures Carried out in the Microbiology Department of General Hospital of Ioannina in 2017

Authors: M. Gerasimou, S. Mantzoukis, P. Christodoulou, N. Varsamis, G. Kolliopoulou, N. Zotos

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Purpose: Microbial infection of the blood is a serious condition where bacteria invade the bloodstream and cause systemic disease. In such cases, blood cultures are performed. Blood cultures are a key diagnostic test for intensive care unit (ICU) patients. Material and method: The BacT/Alert system, which measures the production of carbon dioxide with metabolic organisms, is used. The positive result in the BacT/Alert system is followed by culture in the following selective media: Blood, Mac Conkey No 2, Chocolate, Mueller Hinton, Chapman and Sabaureaud agar. Gram staining method was used to differentiate bacterial species. The microorganisms were identified by biochemical techniques in the automated Microscan (Siemens) system and followed by a sensitivity test on the same system using the minimum inhibitory concentration MIC technique. The sensitivity test is verified by a Kirby Bauer-based test. Results: In 2017 the Laboratory of Microbiology received 3347 blood cultures. Of these, 170 came from the ICU. 116 found positive. Of these S. epidermidis was identified in 42, A. baumannii in 27, K. pneumoniae in 12 (4 of these KPC ‘Klebsiella pneumoniae carbapenemase’), S. hominis in 8, E. faecium in 7, E. faecalis in 5, P. aeruginosa in 3, C. albicans in 3, S. capitis in 2, K. oxytoca in 2, P. mirabilis in 2, E. coli in 1, S. intermidius in 1 and S. lugdunensis in 1. Conclusions: The study of epidemiological data and microbial resistance phenotypes is essential for the choice of therapeutic regimen for the early treatment and limitation of multivalent strains, while it is a crucial factor to solve diagnostic problems.

Keywords: blood culture, bloodstream, infection, intensive care unit

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1262 Short-Term versus Long-Term Effect of Waterpipe Smoking Exposure on Cardiovascular Biomarkers in Mice

Authors: Abeer Rababa'h, Ragad Bsoul, Mohammad Alkhatatbeh, Karem Alzoubi

Abstract:

Introduction: Tobacco use is one of the main risk factors to cardiovascular diseases (CVD) and atherosclerosis in particular. WPS contains several toxic materials such as: nicotine, carcinogens, tar, carbon monoxide and heavy metals. Thus, WPS is considered to be as one of the toxic environmental factors that should be investigated intensively. Therefore, the aim of this study is to investigate the effect of WPS on several cardiovascular biological markers that may cause atherosclerosis in mice. The study also conducted to study the temporal effects of WPS on the atherosclerotic biomarkers upon short (2 weeks) and long-term (8 weeks) exposures. Methods: mice were exposed to WPS and heart homogenates were analyzed to elucidate the effects of WPS on matrix metalloproteinase (MMPs), endothelin-1 (ET-1) and, myeloperoxidase (MPO). Following protein estimation, enzyme-linked immunosorbent assays were done to measure the levels of MMPs (isoforms 1, 3, and 9), MPO, and ET-1 protein expressions. Results: our data showed that acute exposure to WPS significantly enhances the levels of MMP-3, MMP- 9, and MPO expressions (p < 0.05) compared to their corresponding control. However, the body was capable to normalize the level of expressions for such parameters following continuous exposure for 8 weeks (p > 0.05). Additionally, we showed that the level of ET-1 expression was significantly higher upon chronic exposure to WPS compared to both control and acute exposure groups (p < 0.05). Conclusion: Waterpipe exposure has a significant negative effect on atherosclerosis and the enhancement of the atherosclerotic biomarkers expression (MMP-3 and 9, MPO, and ET-1) might represent an early scavenger of compensatory efforts to maintain cardiac function after WP exposure.

Keywords: atherosclerotic biomarkers, cardiovascular disease, matrix metalloproteinase, waterpipe

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1261 The Effect of Coconut Oil on Anthropometric Measurements and Irisin Levels in Overweight Individuals

Authors: Bilge Meral Koc, Elvan Yilmaz Akyuz, Tugce Ozlu

Abstract:

This study aimed to discover the effects of coconut oil intake and diet therapy on anthropometric measurements, biochemical findings and irisin levels in overweight individuals. Materials and Methods: Overweight individuals (n=44, 19-30 years) without any chronic disease were included. In this randomized controlled crossover study, the participants were divided into two groups (Group 1: 23 people, Group 2: 21 people). In the first phase, Group 1 received diet therapy to lose 0.5-1 kg of weight per week and 20 mL of coconut oil/day, while Group 2 only received diet therapy. In the second phase, Group 1 received diet therapy while Group 2 received diet therapy and 20 mL of coconut oil/day. Anthropometric measurements were taken four times. Irisin was measured four times by enzyme-linked immunosorbent (ELISA) method and other biochemical findings were measured twice. Statistical analysis was made on SPSS 20. Results: The irisin level decreased significantly when the participants only took coconut oil (p≤0.05). There was a significant decrease in the participants' body weight, body mass index (BMI) level and body fat percentage (p≤0.01). Insulin, total cholesterol, low density lipoproteins (LDL) cholesterol, and triglyceride (TG) levels of all participants decreased significantly (p≤0.05). There was no significant difference in irisin level due to body weight loss (p≤0.05); coconut oil provided a significant decrease in irisin level (p≤0.05). Conclusion: Diet therapy and weight loss did not have an effect on irisin level, but coconut oil alone was found to reduce irisin level. Coconut oil had no impact on anthropometric and biochemical findings.

Keywords: coconut oil, diet therapy, irisin, overweight

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1260 CCR5 as an Ideal Candidate for Immune Gene Therapy and Modification for the Induced Resistance to HIV-1 Infection

Authors: Alieh Farshbaf, Tayyeb Bahrami

Abstract:

Introduction: Cc-chemokine receptor-5 (CCR5) is known as a main co-receptor in human immunodeficiency virus type-1 (HIV-1) infection. Many studies showed 32bp deletion (Δ32) in CCR5 gene, provide natural resistance to HIV-1 infection in homozygous individuals. Inducing the resistance mechanism by CCR5 in HIV-1 infected patients eliminated many problems of highly-active-anti retroviral therapy (HAART) drugs like as low safety, side-effects and virus rebounding from latent reservoirs. New treatments solved some restrictions that are based on gene modification and cell therapy. Literature review: The stories of the “Berlin and Boston patients” showed autologous hematopoietic stem cells transplantation (HSCT) could provide effective cure of HIV-1 infected patients. Furthermore, gene modification by zinc finger nuclease (ZFN) demonstrated another successful result again. Despite the other studies for gene therapy by ∆32 genotype, there is another mutation -CCR5 ∆32/m303- that provides HIV-1 resistant. It is a heterozygote genotype for ∆32 and T→A point mutation at nucleotide 303. These results approved the key role of CCR5 gene. Conclusion: Recent studies showed immune gene therapy and cell therapy could provide effective cure for refractory disease like as HIV. Eradication of HIV-1 from immune system was not observed by HAART, because of reloading virus genome from latent reservoirs after stopping them. It is showed that CCR5 could induce natural resistant to HIV-1 infection by the new approaches based on stem cell transplantation and gene modifying.

Keywords: CCR5, HIV-1, stem cell, immune gene therapy, gene modification

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1259 Retinal Changes in Patients with Idiopathic Inflammatory Myopathies: A Case-Control Study

Authors: Rachna Agarwal, R. Naveen, Darpan Thakre, Rohit Shahi, Maryam Abbasi, Upendra Rathore, Latika Gupta

Abstract:

Aim: Retinal changes are the window to systemic vasculature. Therefore, we explored retinal changes in patients with idiopathic inflammatory myopathies (IIM) as a surrogate for vascular health. Methods: Adult and juvenile IIM patients visiting a tertiary care centre in 2021 satisfying the International Myositis Classification Criteria were enrolled for detailed ophthalmic examination in comparison with healthy controls (HC). Patients with conditions that precluded thorough posterior chamber examination were excluded. Scale variables are expressed as median (IQR). Multivariate analysis (binary logistic regression-BLR) was conducted, adjusting for age, gender, and comorbidities besides factors significant in univariate analysis. Results: 43 patients with IIM [31 females; age 36 (23-45) years; disease duration 5.5 (2-12) months] were enrolled for participation. DM (44%) was the most common diagnosis. IIM patients exhibited frequent attenuation of retinal vessels (32.6% vs. 4.3%, p <0.001), AV nicking (14% vs. 2.2%, p=0.053), and vascular tortuosity (18.6% vs. 2.2%, p=0.012), besides decreased visual acuity (53.5% vs. 10.9%, p<0.001) and immature cataracts (34.9% vs. 2.2%, p<0.001). Attenuation of vessels [OR 10.9 (1.7-71), p=0.004] emerged as significantly different from HC after adjusting for covariates in BLR. Notably, adults with IIM were more predisposed to retinal abnormalities [21 (57%) vs. 1 (16%), p=0.068], especially attenuation of vessels [14(38%) vs. 0(0), p=0.067] than jIIM. However, no difference was found in retinal features amongst the subtypes of adult IIM, nor did they correlate with MDAAT, MDI, or HAQ-DI. Conclusion: Retinal microvasculopathy and diminution of vision occur in nearly one-third to half of the patients with IIM. Microvasculopathy occurs across subtypes of IIM, and more so in adults, calling for further investigation as a surrogate for damage assessment and potentially even systemic vascular health.

Keywords: idiopathic inflammatory myopathies, vascular health, retinal microvasculopathy, arterial attenuation

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1258 Quality of Life Assessment across the Cancer Continuum: Understanding the Role of an Exercise Rehabilitation Programme

Authors: Bernat-Carles Serdà Ferrer, Arantza Del Valle Gómez

Abstract:

The Quality of Life (QoL) paradigm is multidimensional, dynamic and modular and its definition differs across the cancer continuum. The challenge in the interpretation of QoL data in clinical research is that QoL is influenced by psychological phenomena such as adaptation to illness. This research aims to obtain a valid and sensitive assessment of QoL change over the continuum disease, and to evaluate a rehabilitation programme aimed at inverting the observed decrease in QoL when patients return to daily living activities. The sample comprised 66 men. Patients were first assessed to establish a baseline (P1-diagnosis). This was followed by a post-test (P2-discharge) and a then-test measurement (P3-retrospective evaluation) and after returning home patients were randomized in experimental and control groups. The experimental group attended a rehabilitation programme over 24 weeks (P4). Results show that from baseline to post-test, QoL decreased significantly. The recalibration then-test confirmed a low QoL in all periods evaluated. Significant differences between the experimental and control groups prove the positive effect of the Exercise Rehabilitation Programme (ERP) on QoL. Understanding the real dynamic of QoL over time would help to adapt rehabilitation programmes by improving sensitivity and efficacy and provide professionals with a more accurate perception of the impact of treatment and side effects on patients’ QoL. Our results underline the importance of changing the approach adopted by health professionals towards one of watchful waiting on patients’ QoL until their complete recovery in daily life.

Keywords: exercise, prostate cancer, quality of life, rehabilitation programme, response shift

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1257 Endoscopic Ultrasound-Guided Choledochoduodenostomy in an Advanced Extrahepatic Cholangiocarcinoma

Authors: Diego Carrasco, Catarina Freitas, Hugo Rio Tinto, Ricardo Rio Tinto, Nuno Couto, Joaquim Gago, Carlos Carvalho

Abstract:

Introduction: Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CD) to drain the gallbladder can be a palliative care procedure for non-surgical oncologic patients with cholelithiasis and cholangitis process. Case description: A 59-years old Caucasian male diagnosed with extrahepatic cholangiocarcinoma with multiple liver, lung and peritoneum metastasis, unresponsive to treatment with gemcitabine/cisplatin, presented in the institution with fever, hypotension, and severe upper right abdominal pain secondary to cholelithiasis and cholangitis process. The patient was admitted and started on large spectrum antibiotics plus fluid-challenge. Afterward, a percutaneous transhepatic biliary drainage (PTBD) was performed to drain the gallbladder. This procedure temporarily stabilized the patient. However, the definitive solution required gallbladder removal. Since the patient exhibited an advanced oncologic disease and poor response to the chemotherapy, he was not a candidate for surgical intervention. Diagnostic Pathways: A self-expanding metal stent was placed from the duodenum into the bile duct by endoscopic ultrasound-guided. The stent allowed efficient drainage of the contrast from the gallbladder at the end of the endoscopic procedure. Conclusion and Discussion: The stent allowed efficient drainage of the contrast from the gallbladder at the end of the endoscopic procedure and successfully reversed the cholangitis process. EUS-CD is an effective and safe technique and can be used as a palliative care procedure for non-surgical oncologic patients.

Keywords: palliative care, cholangiocarcinoma, choledochoduodenostomy, endoscopic ultrasound-guided

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1256 The Lived Experiences of Paramedical Students Engaged in Virtual Hands-on Learning

Authors: Zyra Cheska Hidalgo, Joehiza Mae Renon, Kzarina Buen, Girlie Mitrado

Abstract:

ABSTRACT: The global coronavirus disease (COVID-19) has dramatically impacted the lives of many, including education and our economy. Thus, it presents a massive challenge for medical education as instructors are mandated to deliver their lectures virtually to ensure the continuity of the medical education process and ensure students' safety. The purpose of this research paper is to determine the lived experiences of paramedical students who are engaged in virtual hands-on learning and to determine the different coping strategies they used to deal with virtual hands-on learning. The researchers used the survey method of descriptive research design to determine the lived experiences and coping strategies of twenty (20) paramedical students from Lorma Colleges (particularly the College of Medicine Department). The data were collected through online questionnaires, particularly with the use of google forms. This study shows technical issues, difficulty in adapting styles, distractions and time management issues, mental and physical health issues, and lack of interest and motivation are the most common problems and challenges experienced by paramedical students. On the other hand, the coping strategies used by paramedical students to deal with those challenges include time management, engagement in leisure activities, acceptance of responsibilities, studying, and adapting. With the data gathered, the researchers concluded that virtual hands-on learning effectively increases the knowledge of paramedical students. However, teaching and learning barriers must have to be considered to implement virtual hands-on learning successfully.

Keywords: virtual hands-on learning, E-learning, paramedical students, medical education

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1255 Determination of in vitro Antioxidative Activity of Aster yomena (Kitam.) Honda

Authors: Hyun Young Kim, Min Jung Kim, Ji Hyun Kim, Sanghyun Lee, Eun Ju Cho

Abstract:

Oxidative stress that results from overproduction of free radicals can lead to pathogenesis of human diseases including cancer, neurodegenerative diseases, and cardiovascular disease. Aster yomena (Kitam.) Honda (A. yomena) belonging to Compositae family is a perennial plant, and it has anti-inflammatory, anti-asthmatic and anti-obesity effects. In this study, we investigated the antioxidative effect of A. yomena by measuring 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical (˙OH) and superoxide radical (O₂⁻) scavenging activities in vitro. A. yomena was extracted with ethanol and then partitioned with n-hexane, methylene chloride (CH₂Cl₂), ethyl acetate (EtOAc) and n-butanol (n-BuOH). In DPPH radical scavenging assay, the concentration of A. yomena from 10 to 100μg/mL dose-dependently raised the inhibition of DPPH oxidation. Especially, EtOAc fraction of A. yomena showed the highest DPPH radical scavenging activity among other fractions. The ˙OH radical scavenging activities of the extract and four fractions of A. yomena were increased by over 80% at a concentration of 50μg/mL. Especially, the IC50 value of EtOAc fraction was 0.03 μg/mL that is the lowest value compared with the values of other fractions. In addition, we found that the EtOAc fraction of A. yomena was showed to be better at O₂⁻ radical scavenging than other fractions. Taken together these results, we suggested that A. yomena, especially EtOAc fraction, can be used as a natural antioxidant against free radicals. Acknowledgements: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2016R1D1A1B03931593).

Keywords: Aster yomena (Kitam.) Honda (A. yomena), free radicals, antioxidant, EtOAc fraction

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1254 Osteogenesis in Thermo-Sensitive Hydrogel Using Mesenchymal Stem Cell Derived from Human Turbinate

Authors: A. Reum Son, Jin Seon Kwon, Seung Hun Park, Hai Bang Lee, Moon Suk Kim

Abstract:

These days, stem cell therapy is focused on for promising source of treatment in clinical human disease. As a supporter of stem cells, in situ-forming hydrogels with growth factors and cells appear to be a promising approach in tissue engineering. To examine osteogenic differentiation of hTMSCs which is one of mesenchymal stem cells in vivo in an injectable hydrogel, we use a methoxy polyethylene glycol-polycaprolactone blockcopolymer (MPEG-PCL) solution with osteogenic factors. We synthesized MPEG-PCL hydrogel and measured viscosity to check sol-gel transition. In order to demonstrate osteogenic ability of hTMSCs, we conducted in vitro osteogenesis experiment. Then, to confirm the cell cytotoxicity, we performed WST-1 with hTMSCs and MPEG-PCL. As the result of in vitro experiment, we implanted cell and hydrogel mixture into animal model and checked degree of osteogenesis with histological analysis and amount of expression genes. Through these experimental data, MPEG-PCL hydrogel has sol-gel transition in temperature change and is biocompatible with stem cells. In histological analysis and gene expression, hTMSCs are very good source of osteogenesis with hydrogel and will use it to tissue engineering as important treatment method. hTMSCs could be a good adult stem cell source for usability of isolation and high proliferation. When hTMSCs are used as cell therapy method with in situ-formed hydrogel, they may provide various benefits like a noninvasive alternative for bone tissue engineering applications.

Keywords: injectable hydrogel, stem cell, osteogenic differentiation, tissue engineering

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1253 Effect of Zingerone on High-Fructose Diet-Indeuced Metabolic Derangements in Growing Sprague-Dawley Rats

Authors: Nondumiso Lushozi, Busisani Lembede, Eliton Chivandi

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Consumption of fructose increases the risk of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome in children. Zingerone which is found in ginger has antidiabetic and antiobesogenic properties. Therefore, the aim of the study was to investigate the potential of orally administered zingerone to protect growing Sprague-Dawley rats (mimicking growing children) against high-fructose diet-induced metabolic derangements. Forty, 21-day old female Sprague-Dawley rats were randomly allocated and administered the following four treatments for 12 weeks: group I: standard rat chow (SR) + plain water (PW) + plain gelatine cube (PC). group II: SR + 20% (w/v) fructose solution (FS) + PC. group III: SR + FS + 100 mg/kg/day of fenofibrate in gelatine cube. group IV: SR+ FS + 20 mg/kg/day of zingerone in gelatine cube. The rats’ triglyceride, cholesterol, insulin & adiponectin concentration, visceral fat liver lipid content, homoeostasis model assessment of insulin resistance (HOMA-IR) and ability to handle glucose were determined. Oral administration of zingerone significantly increased (P<0.001) visceral fat and liver lipid content (P<0.001), respectively. Results from the study revealed that administration of 20% fructose solution did not induce metabolic dysfunction, however the zingerone treatment increased visceral fat and liver lipid content, all these lipid abnormalities are typical features of the metabolic syndrome, therefore the current study suggests that zingerone has no effect on metabolic dysfunction in adolescent females.

Keywords: antidiabetic, metabolic syndrome, zingerone, antiobesogenic

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1252 Biophysical Consideration in the Interaction of Biological Cell Membranes with Virus Nanofilaments

Authors: Samaneh Farokhirad, Fatemeh Ahmadpoor

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Biological membranes are constantly in contact with various filamentous soft nanostructures that either reside on their surface or are being transported between the cell and its environment. In particular, viral infections are determined by the interaction of viruses (such as filovirus) with cell membranes, membrane protein organization (such as cytoskeletal proteins and actin filament bundles) has been proposed to influence the mechanical properties of lipid membranes, and the adhesion of filamentous nanoparticles influence their delivery yield into target cells or tissues. The goal of this research is to integrate the rapidly increasing but still fragmented experimental observations on the adhesion and self-assembly of nanofilaments (including filoviruses, actin filaments, as well as natural and synthetic nanofilaments) on cell membranes into a general, rigorous, and unified knowledge framework. The global outbreak of the coronavirus disease in 2020, which has persisted for over three years, highlights the crucial role that nanofilamentbased delivery systems play in human health. This work will unravel the role of a unique property of all cell membranes, namely flexoelectricity, and the significance of nanofilaments’ flexibility in the adhesion and self-assembly of nanofilaments on cell membranes. This will be achieved utilizing a set of continuum mechanics, statistical mechanics, and molecular dynamics and Monte Carlo simulations. The findings will help address the societal needs to understand biophysical principles that govern the attachment of filoviruses and flexible nanofilaments onto the living cells and provide guidance on the development of nanofilament-based vaccines for a range of diseases, including infectious diseases and cancer.

Keywords: virus nanofilaments, cell mechanics, computational biophysics, statistical mechanics

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1251 Quality of Life and Self-Assessed Health of Methadone – Maintained Opiate Addicts

Authors: Brajevic-gizdic Igna, Vuletic Gorka

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Introduction: Research in opiate addiction is increasingly indicating the importance of substitution therapy in opiate addicts. Opiate addiction is a chronic relapsing disease that includes craving as a criterion. Craving has been considered a predictor of a relapse, which is defined as a strong desire with an excessive need to take a substance. The study aimed to measure the intensity of craving using the VAS (visual analog scale) in opioid addicts taking the Opioid Substitution Therapy (OST). Method: The total sample compromised of 30 participants in outpatient treatment. Two groups of opiate addicts were considered: Methadone-maintenance and buprenorphine-maintenance addicts. The participants completed the survey questionnaire during the outpatient treatment. Results: The results indicated high levels of cravings in patients during the treatment on OST, which is considered an important destabilization factor in abstinence. Thus, the use of methadone/buprenorphine dose should be considered. Conclusion: These findings provided an objective measurement of methadone /buprenorphine dosage and therapy options. The underdoes of OST can put patients at high risk of relapse, resulting in high levels of craving. Thus, when determining the therapeutic dose of OST, it is crucial to consider patients´ craving. This would achieve stabilization more quickly and avoid relapse in abstinence. Subjective physician assessment and patient’s statement are the main criteria to determine OST dosage. Future studies should use larger sample sizes and focus on the importance of intensity craving measurement on OST to objectify methadone /buprenorphine dosage.

Keywords: abstinence, addicts, methadone, OST, quality of life

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1250 Effects of Folic Acid, Alone or in Combination with Other Nutrients on Homocysteine Level and Cognitive Function in Older People: A Systematic Review

Authors: Jiayan Gou, Kexin He, Xin Zhang, Fei Wang, Liuni Zou

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Background: Homocysteine is a high-risk factor for cognitive decline, and folic acid supplementation can lower homocysteine levels. However, current clinical research results are inconsistent, and the effects of folic acid on homocysteine levels and cognitive function in older people are inconsistent. Objective: The objective of this study is to systematically evaluate the effects of folic acid alone or in combination with other nutrients on homocysteine levels and cognitive function in older adults. Methods: Systematic searches were conducted in five databases, including PubMed, Embase, the Cochrane Library, Web of Science, and CINAHL, from inception to June 1, 2023. Randomized controlled trials were included investigating the effects of folic acid alone or in combination with other nutrients on cognitive function in older people. Results: 17 articles were included, with six focusing on the effects of folic acid alone and 11 examining folic acid in combination with other nutrients. The study included 3,100 individuals aged 60 to 83.2 years, with a relatively equal gender distribution (approximately 51.82% male). Conclusion: Folic acid alone or combined with other nutrients can effectively lower homocysteine level and improve cognitive function in patients with mild cognitive impairment. But for patients with Alzheimer's disease and dementia, the intervention only can reduce the homocysteine level, but the improvement in cognitive function is not significant. In healthy older people, high baseline homocysteine levels (>11.3 μmol/L) and good ω-3 fatty acid status (>590 μmol/L) can enhance the improvement effect of folic acid on cognitive function. This trial has been registered on PROSPERO as CRD42023433096.

Keywords: B-complex vitamins, cognitive function, folic acid, homocysteine

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1249 Preventing Neurodegenerative Diseases by Stabilization of Superoxide Dismutase by Natural Polyphenolic Compounds

Authors: Danish Idrees, Vijay Kumar, Samudrala Gourinath

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by misfolding and aggregation of Cu, Zn superoxide dismutase (SOD1). The use of small molecules has been shown to stabilize the SOD1 dimer and preventing its dissociation and aggregation. In this study, we employed molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) to study the interactions between SOD1 and natural polyphenolic compounds. In order to explore the noncovalent interaction between SOD1 and natural polyphenolic compounds, molecular docking and molecular dynamic (MD) simulations were employed to gain insights into the binding modes and free energies of SOD1-polyphenolic compounds. MM/PBSA methods were used to calculate free energies from obtained MD trajectories. The compounds, Hesperidin, Ergosterol, and Rutin showed the excellent binding affinity in micromolar range with SOD1. Ergosterol and Hesperidin have the strongest binding affinity to SOD1 and was subjected to further characterization. Biophysical experiments using Circular Dichroism and Thioflavin T fluorescence spectroscopy results show that the binding of these two compounds can stabilize SOD1 dimer and inhibit the aggregation of SOD1. Molecular simulation results also suggest that these compounds reduce the dissociation of SOD1 dimers through direct interaction with the dimer interface. This study will be helpful to develop other drug-like molecules which may have the effect to reduce the aggregation of SOD1.

Keywords: amyotrophic lateral sclerosis, molecular dynamics simulation, surface plasmon resonance, superoxide dismutase

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