Search results for: kidney disease
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3967

Search results for: kidney disease

2647 Subacute Toxicity Study of Total Alkaloids of Seeds of Peganum harmala in Female Rat

Authors: Mahdeb Nadia, Ghadjati Nadhra, Bettihi Sara, Daamouche Z. El Youm, Bouzidi Abdelouahab

Abstract:

The effects of subacute administration of total alkaloids of seeds Peganum harmala were studied in female Albino-Wistar rats. After intraperitoneal administration of dose 50 mg/kg for 10 days and 40 mg/kg for 7 days of total alkaloids to the seeds of Peganum harmala (animal treatment lasted 17 days), there were remarkable changes in general appearance and deaths occurred in experimental group. After 17 days a significant reduction was observed in the surviving animals treated with total alkaloid seeds.The Red Blood Cells (RBC), Hematocrit (HCT), Hemoglobin (HGB) and White blood cells (WBCs), show significant reduction in the treated groups. There were no statistical differences in Glutamic-Oxaloacetic Transaminase (GOT), Glutamic-pyruvic Transaminase (GPT) and Alkaline Phosphatase (ALP), total protein, glucose and creatinine observed between groups. However the urea was significantly higher in the treated female rats than the control group. Histological examination of liver showed no histopathological changes. Alkaloids of Peganum harmala showed significant toxicity in female rats.

Keywords: Peganum harmala, rat, liver, kidney, alkaloids, toxicity

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2646 Mesenchymal Stem Cells (MSC)-Derived Exosomes Could Alleviate Neuronal Damage and Neuroinflammation in Alzheimer’s Disease (AD) as Potential Therapy-Carrier Dual Roles

Authors: Huan Peng, Chenye Zeng, Zhao Wang

Abstract:

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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2645 An Audit of Restaging Transurethral Resection of Bladder Tumor (Re-TURBT) Quality in a District General Hospital

Authors: Rizwan Iqbal

Abstract:

Introduction: Re-TURBT has been recommended by international guidelines for patients with non-muscle invasive bladder cancer (NMIBC) who are deemed high-risk. Indications for re-TURBTs remain controversial and studies show mixed outcomes. It should be performed when the initial TURBT specimen lacks detrusor muscle, has tumor stage pT1 or G3/high-grade, or where resection is deemed incomplete. This ensures complete resection of tumors that have a high risk of recurrence as well as accurately identifying any tumors which have been upstaged. The aim of this audit was to evaluate the quality of re-TURBTs in a district general hospital. Method: Data were retrospectively collected from 31 patients who had re-TURBTs between April 2021 and September 2022. Data included baseline demographics, time from initial to re-TURBT, quality of operation note, presence of residual tumor, complications, and administration of chemotherapy within 24 hours of the initial TURBT. Data collection remains ongoing at the time of writing. Results: The mean age was 76 years old and 71.0% of patients were male. 32.3% of patients had their re-TURBT within six weeks and 32.3% had intravesical chemotherapy administered within 24 hours of the initial TURBT. 74.2% of initial TURBTs had detrusor muscle present in the specimen. 48.4% of patients had residual disease following re-TURBT. Just one patient had their pathology upstaged at re-TURBT. The use of the TURBT proforma on the operation note was variable, with 51.6% and 38.7% of surgeons using the proforma after the initial and re-TURBT. Conclusion: Re-TURBT improves bladder cancer staging and is necessary in patients who are deemed high-risk in order to identify any upstaging or recurrence of the disease.

Keywords: urology, bladder cancer, turbt, cancer

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2644 Evaluation of Gene Expression after in Vitro Differentiation of Human Bone Marrow-Derived Stem Cells to Insulin-Producing Cells

Authors: Mahmoud M. Zakaria, Omnia F. Elmoursi, Mahmoud M. Gabr, Camelia A. AbdelMalak, Mohamed A. Ghoneim

Abstract:

Many protocols were publicized for differentiation of human mesenchymal stem cells (MSCS) into insulin-producing cells (IPCs) in order to excrete insulin hormone ingoing to treat diabetes disease. Our aim is to evaluate relative gene expression for each independent protocol. Human bone marrow cells were derived from three volunteers that suffer diabetes disease. After expansion of mesenchymal stem cells, differentiation of these cells was done by three different protocols (the one-step protocol was used conophylline protein, the two steps protocol was depending on trichostatin-A, and the three-step protocol was started by beta-mercaptoethanol). Evaluation of gene expression was carried out by real-time PCR: Pancreatic endocrine genes, transcription factors, glucose transporter, precursor markers, pancreatic enzymes, proteolytic cleavage, extracellular matrix and cell surface protein. Quantitation of insulin secretion was detected by immunofluorescence technique in 24-well plate. Most of the genes studied were up-regulated in the in vitro differentiated cells, and also insulin production was observed in the three independent protocols. There were some slight increases in expression of endocrine mRNA of two-step protocol and its insulin production. So, the two-step protocol was showed a more efficient in expressing of pancreatic endocrine genes and its insulin production than the other two protocols.

Keywords: mesenchymal stem cells, insulin producing cells, conophylline protein, trichostatin-A, beta-mercaptoethanol, gene expression, immunofluorescence technique

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2643 Patterns of Self-Reported Overweight, Obesity, and Other Chronic Diseases Among University Students in the United Arab Emirates: A Cross-Sectional Study

Authors: Maryam M. Bashir, Luai A. Ahmed, Meera R. Alshamsi, Sara Almahrooqi, Taif Alyammahi, Shooq A. Alshehhi, Waad I. Alhammadi, Fatima H. Alhammadi, Hind A. Alhosani, Rami H. Al-Rifai, Fatma Al-Maskari

Abstract:

Obesity in the Middle East and North Africa (MENA) region has exponentially increased over the past five decades due to rapid urbanization and unhealthy lifestyle changes. It has been well established that overweight and obesity increase the risk of non-communicable diseases (NCDs) and are the leading cause of mortality and economic burden locally, and globally. In the United Arab Emirates (UAE), there is a growing epidemic of obesity and other chronic diseases like type 2 diabetes mellitus and cardiovascular diseases. Prevalence of overweight and obesity in UAE range up to 70% depending on the group being studied. Hence, there is a need to explore their patterns in the country for more targeted and responsive interventions. Our study aimed to explore the patterns of overweight and obesity and some self-reported chronic diseases among university students in Abu Dhabi, the capital city of UAE. A validated online self-administered questionnaire was used to collect data from UAE University (UAEU) students, 18years and above, from August to September 2021. Students’ characteristics were summarized using appropriate descriptive statistics. Overweight, obesity and self-reported chronic diseases were described and compared between male and female students using chi-square and t tests. Other associated factors were also explored in relation to overweight and obesity. All analyses were conducted using STATA statistical software version 16.1 (StataCorp LLC, College Station, TX, USA). 902 students participated in the study. 79.8% were females and mean age was 21.90 ± 5.19 years. Majority of the respondents were undergraduate students (80.71%). The prevalence of self-reported chronic diseases was 22.95%. Obesity (BMI≥30kg/m2), Diabetes Mellitus, and Asthma/Allergies were the commonest diseases (12.48%, 4.21% & 3.22%, respectively). Approximately 5% of the students reported more than one chronic disease. Out of the 833 participating students who had complete weight and height data, prevalence of overweight and obesity was 34.81% (22.33% and 12.48%, respectively). More than half of the male students (54.36%) were overweight or obese. This is significantly higher than in female students (30.56%, p=0.001). Overweight/obesity when compared to normal weight is associated with increasing mean age [23.40 vs 21.01, respectively (p=0.001)]. In addition to gender and age, being married [57.63% vs 31.05% (p=0.001)], being a postgraduate student [51.59% vs 30.92% (p=0.001)] and having two or more chronic diseases [65.85% vs 33.21% (p=0.001)] were also significantly associated with overweight/obesity. Our study showed that almost a quarter of the participating university students reported at least one chronic disease. Obesity was the commonest and more than 1 in 3 students were either overweight or obese. This shows the need for intensive health promotion and screening programs on obesity and other chronic diseases to meet the health needs of these students. This study is also a basis for further research, especially qualitative, to explore the relevant risk factors and risk groups for more targeted interventions.

Keywords: chronic disease, obesity, overweight, students, United Arab Emirates

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2642 Serum Potassium Before, During and After Exercise at 70% Maximal Heart Rate: The Safe Exercise Dosage Across Different Parameters of Health and Fitness Level

Authors: Omar bin Mihat

Abstract:

The number of sudden deaths is increasing over the past years. These deaths occur not during physical activities but upon cessation. Post-mortem confirms these deaths as cardiac arrest non-specifically. Congenital heart disease is a condition undiagnosed whereby only surface upon physical exertion leading to sudden death is unavoidable. Channelopathy, a condition that refers to any disease from the defect in iron-channel function, particularly the sodium-potassium pump, during the cessation of the exercise can be controlled. The derivation of heart rate return (HRrtn) is a procedure of a control cooling down process according to the heart rate (HR). Empirically, potassium rises linearly with intensity and falls sharply upon abrupt cessation of exertion, resulting in fatal arrhythmia due to hypokalaemia. It is vital that the flux of potassium should be maintained within the normal range during physical activities. To achieve this, the dosage of physical exertion (exercise) should be identified. Various percentages of the intensity of maximum heart rate (MHR) will precipitate different adaptations and remodeling of various organs. 70% of MHR will surface physiological adaptations, including enhancement of endurance, fitness level, and general health, and there was no significant rise of serum potassium (K+) during the entire phase of the treadmill brisk walk at a different rate of perceived exertion (RPE) from the subject of various fitness background. There was also no significant rise in blood pressure (BP) during the entire phase of the treadmill brisk walk, substantiating 70% MHR is the safe dosage across different parameters of health and fitness level.

Keywords: potassium, maximal heart rate, exercise dosage, fitness level

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2641 Nutritional Status of People Living with Human Immuno Virus/Acquired Immune Deficiency Syndrome Attending Anti-Retro Viral Treatment Clinic of BP Koirala Institute of Health Sciences, Nepal

Authors: Ghimire K., Mehta R. S., Parajuli P., Chettri R.

Abstract:

Background: Malnutrition is a common hallmark of Human Immuno Virus (HIV) disease. It plays a synergistic role in immunosuppression which is initiated by Human Immuno Virus itself, and malnutrition forms an independent risk factor for disease progression. Objectives: The objective of the study is to assess the nutritional status of the people living with Human Immuno Virus/Acquired Immune Deficiency Syndrome attending the Anti-Retro viral Treatment Clinic and find the association of nutritional status with different socio-demographic variables. Methods: A total of 101 people living with HIV/AIDS (PLWHA) were selected by convenient sampling technique. The study was conducted at the ART clinic of BPKIHS. A subjective global assessment tool was used for data collection. Descriptive and inferential statistics were used for data analysis. Results: The study demonstrated that the mean age of the respondents was 40.97+8.650 years. 65.3% were well-nourished, and 34.7% of the participants were mildly/moderately malnourished, whereas none of them were severely malnourished. BMI was statistically significant with education status, family income, and duration of illness of the participants, and nutritional status was statistically significant with gender, marital status, education status, and family history of HIV. Conclusion: On the basis of the result, it can be concluded that more than half of the respondents were well nourished. Gender, marital status, and education are associated with nutritional status.

Keywords: nutritional status, people living with HIV/AIDS, ART treatment, Nepal

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2640 Altered Expression of Ubiquitin Editing Complex in Ulcerative Colitis

Authors: Ishani Majumdar, Jaishree Paul

Abstract:

Introduction: Ulcerative Colitis (UC) is an inflammatory disease of the colon resulting from an autoimmune response towards individual’s own microbiota. Excessive inflammation is characterized by hyper-activation of NFkB, a transcription factor regulating expression of various pro-inflammatory genes. The ubiquitin editing complex consisting of TNFAIP3, ITCH, RNF11 and TAX1BP1 maintains homeostatic levels of active NFkB through feedback inhibition and assembles in response to various stimuli that activate NFkB. TNFAIP3 deubiquitinates key signaling molecules involved in NFkB activation pathway. ITCH, RNF11 and TAX1BP1 provide substrate specificity, acting as adaptors for TNFAIP3 function. Aim: This study aimed to find expression of members of the ubiquitin editing complex at the transcript level in inflamed colon tissues of UC patients. Materials and Methods: Colonic biopsy samples were collected from 30 UC patients recruited at Department of Gastroenterology, AIIMS (New Delhi). Control group (n= 10) consisted of individuals undergoing examination for functional disorders. Real Time PCR was used to determine relative expression with GAPDH as housekeeping gene. Results: Expression of members of the ubiquitin editing complex was significantly altered during active disease. Expression of TNFAIP3 was upregulated while concomitant decrease in expression of ITCH, RNF11, TAX1BP1 was seen in UC patients. Discussion: This study reveals that increase in expression of TNFAIP3 was unable to control inflammation during active UC. Further, insufficient upregulation of ITCH, RNF11, TAX1BP1 may limit the formation of the ubiquitin complex and contribute to pathogenesis of UC.

Keywords: altered expression, inflammation, ubiquitin editing complex, ulcerative colitis

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2639 STAT6 Mediates Local and Systemic Fibrosis and Type Ii Immune Response via Macrophage Polarization during Acute and Chronic Pancreatitis in Murine Model

Authors: Hager Elsheikh, Matthias Sendler, Juliana Glaubnitz

Abstract:

In pancreatitis, an inflammatory reaction occurs in the pancreatic secretory cells due to premature activation of proteases, leading to pancreatic self-digestion and necrotic cell death of acinar cells. Acute pancreatitis in patients is characterized by a severe immune reaction that could lead to serious complications, such as organ failure or septic shock, if left untreated. Chronic pancreatitis is a recurrence of episodes of acute pancreatitis resulting in a fibro-inflammatory immune response, in which the type 2 immune response is primarily driven by AAMs in the pancreas. One of the most important signaling pathways for M2 macrophage activation is the IL-4/STAT6 pathway. Pancreatic fibrosis is induced by the hyperactivation of pancreatic stellate cells by dysregulation in the inflammatory response, leading to further damage, autodigestion and possibly necrosis of pancreatic acinar cells. The aim of this research is to investigate the effect of STAT6 knockout in disease severity and development of fibrosis wound healing in the presence of different macrophage populations, regulated by the type 2 immune response, after inducing chronic and/or acute pancreatitis in mice models via cerulean injection. We further investigate the influence of the JAK/STAT6 signaling pathway on the balance of fibrosis and regeneration in STAT6 deficient and wild-type mice. The characterization of resident and recruited macrophages will provide insight into the influence of the JAK/STAT6 signaling pathway on infiltrating cells and, ultimately, tissue fibrosis and disease severity.

Keywords: acute and chronic pancreatitis, tissue regeneration, macrophage polarization, Gastroenterology

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2638 Monitoring Prolong Use of Intravenous Antibiotics: Antimicrobial Stewardship

Authors: Komal Fizza

Abstract:

Irrational and non-judicious use of antibiotics pave the way for an upsurge in antibiotic resistance, diminished effectiveness of different therapeutic regimens and as well as impounding effect on disease management leading to further morbidities. In the backdrop of this the current research is aimed to assess whether antimicrobial prescribing is in accordance with the Infectious Disease Society of America Guidelines in hospitalized patients at Shifa International Hospital, Islamabad, Pakistan. Shifa International Hospital, Islamabad is a 500 bed hospital. With the help of MIS team a form wad developed that gave the information about medical records number, name of the patient, day of start of antibiotic, the day antibiotic is supposed to be stopped and as well as the diagnosis of the patient. A ward pharmacist was employed to generate this report on a daily basis. The therapeutic regiment was reviewed by the pharmacist by monitoring the clinical progress, laboratory report and diagnosis. On the basis of this information, pharmacist made suggestions and forwarded to the hospital doctors responsible for prescribing antibiotics. If desired, changes were made regularly. In the current research our main focus was to implement this action and therefore, started monitoring patients who were on antibiotic regimens for more than 10-15 days. We took this initiative since November, 2013. At the start of the program a maximum 19 patients/day were reported to be on antibiotic regimen for more than 10-15 days. After the implementation of the initiative, the number of patients was decreased to fifteen patients per day in December, further decreased to 7 in the month of January and 9 and 6 in February and March respectively. The average patient census was 350. The current pilot study highlighted the role of pharmacist in initiating antibiotic stewardship programs in hospital settings.

Keywords: stewardship, antibiotics, resistance, clinical process

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2637 Anthelminthic Effect of Clitoria Ternatea on Paramphistomum Cervi in Buffalo (Bubalus Bubalis) of Udaipur, Rajasthan, India

Authors: Bhanupriya Sanger, Kiran Roat, Gayatri Swarnakar

Abstract:

Helminths including Paramphistomum Cervi (P. cervi) are a major cause of reduced production in livestock or domestic ruminant. Rajasthan is the largest state of India having a maximum number of livestock. The economy of rural people largely depends on livestock such as cow, buffalo, goat and sheep. The prevalence of P. cervi helminth parasite is extremely high in buffalo (Bubalus bubalis) of Udaipur, which causes the disease paramphistomiasis. This disease mainly affects milk, meat, wool production and loss of life of buffalo. Chemotherapy is the only efficient and effective tool to cure and control the helminth P. cervi infection, as efficacious vaccines against helminth have not been developed so far. Various veterinary drugs like Albendazole have been used as the standard drug for eliminating P. cervi from buffalo, but these drugs are unaffordable and inaccessible for poor livestock farmers. The fruits, leaves and seeds of Clitoria ternatea Linn. are known for their ethno-medicinal value and commonly known as “Aprajita” in India. Seed extract of Clitoria ternatea found to have a significant anthelmintic action against Paramphistomum cervi at the dose of 35 mg/ml. The tegument of treated P. cervi was compared with controlled parasites by light microscopy. Treated P. cervi showed extensive distortion and destruction of the tegument including ruptured parenchymal cells, disruption of musculature cells, swelling and vacuolization in tegumental and sub tegumental cells. As a result, it can be concluded that the seeds of Clitoria ternatea can be used as the anthelmintic agent. Key words: Paramphistomiasis, Buffalo, Alcoholic extract, Paramphistomum cervi, Clitoria ternatea.

Keywords: buffalo, Clitoria ternatea, Paramphistomiasis, Paramphistomum cervi

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2636 Antioxidative Effect of Bauhinia acuminata Water Extract Consumption in Rat

Authors: Amornnat Thuppia, Pornrut Rabintossaporn, Suphaket Saenthaweesuk, Nuntiya Somparn

Abstract:

The aim of this present study was to determine the antioxidant effects and its mechanism of aqueous leaves extract of Bauhinia acuminata (BA) in rat. The extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with the extract at the dose of 50, 100 and 200 mg/kg for 28 days. Phytochemical screening of plant extracts showed the presence of saponin, alkaloid, cardiac glycosides, flavonoids, tannin and steroid compounds. The extract contained phenolic compounds 53.36 ± 1.01 mg of gallic acid equivalents per gram BA extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 44.47 ± 2.83 µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14µg/mL. In the animals, the extract was well tolerated by the animals throughout the 28 days of study as shown by normal serum levels AST, ALP, ALT, BUN and Cr as well as normal histology of liver and pancreatic and kidney tissue. Significantly, reduction of serum oxidative stress markers malondialdehyde (MDA) was found in rat treated with BA extract compared with control. Taken together, this study provides evidence that Bauhinia acuminata (BA) exhibits direct antioxidant properties and induces cytoprotective enzyme in vivo.

Keywords: Bauhinia acuminata, antioxidant, malondialdehyde (MDA), oxidative marker

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2635 Dissection of Genomic Loci for Yellow Vein Mosaic Virus Resistance in Okra (Abelmoschus esculentas)

Authors: Rakesh Kumar Meena, Tanushree Chatterjee

Abstract:

Okra (Abelmoschus esculentas L. Moench) or lady’s finger is an important vegetable crop belonging to the Malvaceae family. Unfortunately, production and productivity of Okra are majorly affected by Yellow Vein mosaic virus (YVMV). The AO: 189 (resistant parent) X AO: 191(susceptible parent) used for the development of mapping population. The mapping population has 143 individuals (F₂:F₃). Population was characterized by physiological and pathological observations. Screening of 360 DNA markers was performed to survey for parental polymorphism between the contrasting parents’, i.e., AO: 189 and AO: 191. Out of 360; 84 polymorphic markers were used for genotyping of the mapping population. Total markers were distributed into four linkage groups (LG1, LG2, LG3, and LG4). LG3 covered the longest span (106.8cM) with maximum number of markers (27) while LG1 represented the smallest linkage group in terms of length (71.2cM). QTL identification using the composite interval mapping approach detected two prominent QTLs, QTL1 and QTL2 for resistance against YVMV disease. These QTLs were placed between the marker intervals of NBS-LRR72-Path02 and NBS-LRR06- NBS-LRR65 on linkage group 02 and linkage group 04 respectively. The LOD values of QTL1 and QTL2 were 5.7 and 6.8 which accounted for 19% and 27% of the total phenotypic variation, respectively. The findings of this study provide two linked markers which can be used as efficient diagnostic tools to distinguish between YVMV resistant and susceptible Okra cultivars/genotypes. Lines identified as highly resistant against YVMV infection can be used as donor lines for this trait. This will be instrumental in accelerating the trait improvement program in Okra and will substantially reduce the yield losses due to this viral disease.

Keywords: Okra, yellow vein mosaic virus, resistant, linkage map, QTLs

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2634 The Effect of Eight-Week Medium Intensity Interval Training and Curcumin Intake on ICMA-1 and VCAM-1 Levels in Menopausal Fat Rats

Authors: Abdolrasoul Daneshjoo, Fatemeh Akbari Ghara

Abstract:

Background and Purpose: Obesity is an increasing factor in cardiovascular disease and serum levels of cellular adhesion molecule. It plays an important role in predicting risk for coronary artery disease. The purpose of this research was to study the effect of eight weeks moderate intensity interval training and curcumin intake on ICAM-1 & VCAM-1 levels of menopausal fat rats. Materials and methods: in this study, 28 Wistar Menopausal fat rats aged 6-8 weeks with an average weight of 250-300 (gr) were randomly divided into four groups: control, curcumin supplement, moderate intensity interval training and moderate intensity interval training + curcumin supplement. (7 rats each group). The training program was planned as 8 weeks and 3 sessions per week. Each session consisted of 10 one-min sets with 50 percent intensity and the 2-minutes interval between sets in the first week. Subjects started with 14 meters per minute, and 2 (m/min) was added to increase their speed weekly until the speed of 28 (m/min) in the 8th week. Blood samples were taken 48 hours after the last training session, and ICAM-1 A and VCAM-1 levels were measured. SPSS software, one-way analysis of variance (ANOVA) and Pearson correlation coefficient were used to assess the results. Results: The results showed that eight weeks of training and taking curcumin had significant effects on ICAM-1 levels of the rats (p ≤ 0.05). However, it had no significant effect on VCAM-1 levels in menopausal obese rates (p ≥ 0.05). There was no significant correlation between the levels of ICAM-1 and VCAM-1 in eight weeks training and taking curcumin. Conclusion: Implementation of moderate intensity interval training and the use of curcumin decreased ICAM-1 significantly.

Keywords: curcumin, interval training , ICMA, VCAM

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2633 Double-Spear 1-H2-1 Oncolytic-Immunotherapy for Refractory and Relapsing High-Risk Human Neuroblastoma and Glioma

Authors: Lian Zeng

Abstract:

Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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2632 Obtaining Norms for Arabic Translated Version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychological Battery in Normal Elderly Omanis Attending a Tertiary Hospital in Oman

Authors: Ammar Alobaidy, Lamees Alsawafi, Malak Almawali, Balqees Alabri, Hajer Alhamrashdi

Abstract:

Background: There is scarce data in the literature concerning the use of Arabic version neuron psychological cognitive tests in the geriatric age group of the Omani population. Objectives: Our aim is to obtain norms for normal elderly Omanis assessed by The Consortium to Establish a Registry for Alzheimer's disease (CERAD) neuro psychological battery and to compare these norms with other studies in the literature. Methods: 84 attendants and visitors of in-patients at Sultan Qaboos University Hospital, elder than 55 years, were interviewed. All participants were assessed by Dementia Rating Scale & Geriatric Depression Scale to ensure the integrity of their activities of daily living and the absence of depression, respectively. The performance of all participants in the CERAD battery was rated by a single rater to optimize the inter-rater reliability. Results: The cut-point for average performance in CERAD battery is dependent on the age, sex, and level of education and cannot be set as a single cut-point for all elderly Omanis. Conclusion: This study has shown the effect of age, sex, and level of education on the cognitive performance of normal elderly Omanis. The normative data obtained from this study can be utilized to differentiate between the cognitive decline of normal aging and the cognitive impairment due to various neuro cognitive disorders in the elderly Omanis, and probably culturally similar Arabic speaking communities.

Keywords: CERAD, neuropsychological battery, normal aging, elderly Omanis

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2631 Building a Framework for Digital Emergency Response System for Aged, Long Term Care and Chronic Disease Patients in Asia Pacific Region

Authors: Nadeem Yousuf Khan

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This paper proposes the formation of a digital emergency response system (dERS) in the aged, long-term care, and chronic disease setups in the post-COVID healthcare ecosystem, focusing on the Asia Pacific market where the aging population is increasing significantly. It focuses on the use of digital technologies such as wearables, a global positioning system (GPS), and mobile applications to build an integrated care system for old folks with co-morbidities and other chronic diseases. The paper presents a conceptual framework of a connected digital health ecosystem that not only provides proactive care to registered patients but also prevents the damages due to sudden conditions such as strokes by alerting and treating the patients in a digitally connected and coordinated manner. A detailed review of existing digital health technologies such as wearables, GPS, and mobile apps was conducted in context with the new post-COVID healthcare paradigm, along with a detailed literature review on the digital health policies and usability. A good amount of research papers is available in the application of digital health, but very few of them discuss the formation of a new framework for a connected digital ecosystem for the aged care population, which is increasing around the globe. A connected digital emergency response system has been proposed by the author whereby all registered patients (chronic disease and aged/long term care) will be connected to the proposed digital emergency response system (dERS). In the proposed ecosystem, patients will be provided with a tracking wrist band and a mobile app through which the control room will be monitoring the mobility and vitals such as atrial fibrillation (AF), blood sugar, blood pressure, and other vital signs. In addition to that, an alert in case if the patient falls down will add value to this system. In case of any variation in the vitals, an alert is sent to the dERS 24/7, and dERS clinical staff immediately trigger that alert which goes to the connected hospital and the adulatory service providers, and the patient is escorted to the nearest connected tertiary care hospital. By the time, the patient reaches the hospital, dERS team is ready to take appropriate clinical action to save the life of the patient. Strokes or myocardial infarction patients can be prevented from disaster if they are accessible to engagement healthcare. This dERS will play an effective role in saving the lives of aged patients or patients with chronic co-morbidities.

Keywords: aged care, atrial fibrillation, digital health, digital emergency response system, digital technology

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2630 Ingini Seeds: A Qualitative Study on Its Use in Water Purification in the Dry Zone of Sri Lanka

Authors: Iranga Weerakkody, Palitha Sri Geegana Arachchige, Dasith Tilakaratna

Abstract:

The aim of this research is to study how folk wisdom can be applied to assist in the process of purification of water. This is qualitative research, and by random sampling, it is focused on to the dry zone of Sri Lanka. The research limitation has been set to the use of Ingini seeds (Strychnos potatorum) to purify water. Here the research is based on connecting traditional knowledge regarding water purification using Ingini seeds to modern times and the advantages and disadvantages of using Ingini seeds to purify water sources. Ingini seeds have been used among villagers of the dry zone to purify water for a long time by methods such as planting Ingini plants around water sources and depositing seeds covered with a cotton cloth inside wells. Crushed Ingini seeds have been put into clay water pots to reduce the hardness of water, as well as the number of impurities present in the water. This shows that Ingini seeds have a property that is successful in precipitating dissolved impurities in water. Ingini seeds are also used to precipitate solid impurities in herbal wine. The advantages of using Ingini seeds are that it can be obtained naturally from the ecology without an additional cost and that it is completely organic forest produce. Another specialty is that in practices, it is used to treat kidney stones and other water-related diseases affecting the kidneys.

Keywords: folklife, Ingini seeds, Strychnos potatorum, organic forest produce, water purification

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2629 Plasma Electrolytes and Gamma Glutamyl Transpeptidase (GGT) Status in Dementia Subjects in Southern Nigeria

Authors: Salaam Mujeeb, Adeola Segun, Abdullahi Olasunkanmi

Abstract:

Dementia is becoming a major concern as the world population is increasing and elderly populations are being neglected. Liver and kidney Diseases have been implicated as risk factors in the etiology of Dementia. This study, therefore, evaluates the plasma Gamma Glutamyl Transferase (GGT) activity and plasma Electrolytes in other to find an association between the biomarkers and Dementia. The subjects (38) were age and sex-matched with their corresponding controls and structured questionnaires were used to obtain medical information. Using spectrophotometric and ion selective Electrode techniques respectively, we found and elevated GGT activity in the Dementia Subjects. Remarkably, no association was found between the plasma Electrolytes level and Dementia subjects. It was also observed that severity of Dementia worsens with age. Moreover, the condition of the dementia subjects worsens with reducing weight. Furthermore, the presence of Comorbidity e.g. Hypertension, Obesity, Diabetes and Habits like Smoking, Drugs and Alcohol consumption interferes with Electrolyte balance. Weight loss monitoring and IBM check are advised in Elderly individuals particularly females as they may be inductive of early or future cognitive impairments. Therefore, it might be useful as an early detection tool. Government and society should invest more on the Geriatric population by establishing Old people's home and providing social care services.

Keywords: clinical characteristics, dementia, electrolytes, gamma glutamyl transpeptidase, GGT

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2628 The Lopsided Burden of Non-Communicable Diseases in India: Evidences from the Decade 2004-2014

Authors: Kajori Banerjee, Laxmi Kant Dwivedi

Abstract:

India is a part of the ongoing globalization, contemporary convergence, industrialization and technical advancement that is taking place world-wide. Some of the manifestations of this evolution is rapid demographic, socio-economic, epidemiological and health transition. There has been a considerable increase in non-communicable diseases due to change in lifestyle. This study aims to assess the direction of burden of disease and compare the pressure of infectious diseases against cardio-vascular, endocrine, metabolic and nutritional diseases. The change in prevalence in a ten-year period (2004-2014) is further decomposed to determine the net contribution of various socio-economic and demographic covariates. The present study uses the recent 71st (2014) and 60th (2004) rounds of National Sample Survey. The pressure of infectious diseases against cardio-vascular (CVD), endocrine, metabolic and nutritional (EMN) diseases during 2004-2014 is calculated by Prevalence Rates (PR), Hospitalization Rates (HR) and Case Fatality Rates (CFR). The prevalence of non-communicable diseases are further used as a dependent variable in a logit regression to find the effect of various social, economic and demographic factors on the chances of suffering from the particular disease. Multivariate decomposition technique further assists in determining the net contribution of socio-economic and demographic covariates. This paper upholds evidences of stagnation of the burden of communicable diseases (CD) and rapid increase in the burden of non-communicable diseases (NCD) uniformly for all population sub-groups in India. CFR for CVD has increased drastically in 2004-2014. Logit regression indicates the chances of suffering from CVD and EMN is significantly higher among the urban residents, older ages, females, widowed/ divorced and separated individuals. Decomposition displays ample proof that improvement in quality of life markers like education, urbanization, longevity of life has positively contributed in increasing the NCD prevalence rate. In India’s current epidemiological phase, compression theory of morbidity is in action as a significant rise in the probability of contracting the NCDs over the time period among older ages is observed. Age is found to play a vital contributor in increasing the probability of having CVD and EMN over the study decade 2004-2014 in the nationally representative sample of National Sample Survey.

Keywords: cardio-vascular disease, case-fatality rate, communicable diseases, hospitalization rate, multivariate decomposition, non-communicable diseases, prevalence rate

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2627 Genome-Wide Identification and Characterization of MLO Family Genes in Pumpkin (Cucurbita maxima Duch.)

Authors: Khin Thanda Win, Chunying Zhang, Sanghyeob Lee

Abstract:

Mildew resistance locus o (Mlo), a plant-specific gene family with seven-transmembrane (TM), plays an important role in plant resistance to powdery mildew (PM). PM caused by Podosphaera xanthii is a widespread plant disease and probably represents the major fungal threat for many Cucurbits. The recent Cucurbita maxima genome sequence data provides an opportunity to identify and characterize the MLO gene family in this species. Total twenty genes (designated CmaMLO1 through CmaMLO20) have been identified by using an in silico cloning method with the MLO gene sequences of Cucumis sativus, Cucumis melo, Citrullus lanatus and Cucurbita pepo as probes. These CmaMLOs were evenly distributed on 15 chromosomes of 20 C. maxima chromosomes without any obvious clustering. Multiple sequence alignment showed that the common structural features of MLO gene family, such as TM domains, a calmodulin-binding domain and 30 important amino acid residues for MLO function, were well conserved. Phylogenetic analysis of the CmaMLO genes and other plant species reveals seven different clades (I through VII) and only clade IV is specific to monocots (rice, barley, and wheat). Phylogenetic and structural analyses provided preliminary evidence that five genes belonged to clade V could be the susceptibility genes which may play the importance role in PM resistance. This study is the first comprehensive report on MLO genes in C. maxima to our knowledge. These findings will facilitate the functional analysis of the MLOs related to PM susceptibility and are valuable resources for the development of disease resistance in pumpkin.

Keywords: Mildew resistance locus o (Mlo), powdery mildew, phylogenetic relationship, susceptibility genes

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2626 Caregivers Burden: Risk and Related Psychological Factors in Caregivers of Patients with Parkinson’s Disease

Authors: Pellecchia M. T., Savarese G., Carpinelli L., Calabrese M.

Abstract:

Introduction: Parkinson's disease (PD) is characterized by a progressive loss of autonomy which undoubtedly has a significant impact on the quality of life of caregivers, and parents are the main informal caregivers. Caring for a person with PD is associated with an increased risk of psychiatric morbidity and persistent anxiety-depressive distress. The aim of the study is to investigate the burden on caregivers of patients with PD, through the use of multidimensional scales and to identify their personological and environmental determinants. Methods: The study has been approved by the Ethic Committee of the University of Salerno and informed consent for participation to the study was obtained from patients and their caregivers. The study was conducted at the Neurology Department of the A.O.U. "San Giovanni di Dio and Ruggi D’Aragona" of Salerno between September 2020 and May 2021. Materials: The questionnaires used were: a) Caregiver Burden Inventory - CBI a questionnaire of 24 items that allow identifying five sub-categories of burden (objective, psychological, physical, social, emotional); b) Depression Anxiety Stress Scales Short Version - DASS-21 questionnaire consisting of 21 items and valid in examining three distinct but interrelated areas (depression, anxiety and stress); c) Family Strain Questionnaire Short Form - FSQ-SF is a questionnaire of 30 items grouped in areas of increasing psychological risk (OK, R, SR, U); d) Zarit Caregiver Burden Inventory - ZBI, consisting of 22 items based on the analysis of two main factors: personal stress and pressure related to his role; e) Life Satisfaction, a single item that aims to evaluate the degree of life satisfaction in a global way using a 0-100 Likert scale. Findings: N ° 29 caregivers (M age = 55.14, SD = 9.859; 69% F) participated in the study. 20.6% of the sample had severe and severe burden (CBI score = M = 26.31; SD = 22.43) and 13.8% of participants had moderate to severe burden (ZBI). The FSQ-SF highlighted a minority of caregivers who need psychological support, in some cases urgent (Area SR and Area U). The DASS-21 results show a prevalence of stress-related symptoms (M = 10.90, SD = 10.712) compared to anxiety (M = 7.52, SD = 10.752) and depression (M = 8, SD = 10.876). There are significant correlations between some specific variables and mean test scores: retired caregivers report higher ZBI scores (p = 0.423) and lower Life Satisfaction levels (p = -0.460) than working caregivers; years of schooling show a negative linear correlation with the ZBI score (p = -0.491). The T-Test indicates that caregivers of patients with cognitive impairment are at greater risk than those of patients without cognitive impairment. Conclusions: It knows the factors that affect the burden the most would allow for early recognition of risky situations and caregivers who would need adequate support.

Keywords: anxious-depressive axis, caregivers’ burden, Parkinson’ disease, psychological risks

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2625 A Lightning Strike Mimic: The Abusive Use of Dog Shock Collar Presents as Encephalopathy, Respiratory Arrest, Cardiogenic Shock, Severe Hypernatremia, Rhabdomyolysis, and Multiorgan Injury

Authors: Merrick Lopez, Aashish Abraham, Melissa Egge, Marissa Hood, Jui Shah

Abstract:

A 3 year old male with unknown medical history presented initially with encephalopathy, intubated for respiratory failure, and admitted to the pediatric intensive care unit (PICU) with refractory shock. During resuscitation in the emergency department, he was found to be in severe metabolic acidosis with a pH of 7.03 and escalated on vasopressor drips for hypotension. His initial sodium was 174. He was noted to have burn injuries to his scalp, forehead, right axilla, bilateral arm creases and lower legs. He had rhabdomyolysis (initial creatinine kinase 5,430 U/L with peak levels of 62,340 normal <335 U/L), cardiac injury (initial troponin 88 ng/L with peak at 145 ng/L, normal <15ng/L), hypernatremia (peak 174, normal 140), hypocalcemia, liver injury, acute kidney injury, and neuronal loss on magnetic resonance imaging (MRI). Soft restraints and a shock collar were found in the home. He was critically ill for 8 days, but was gradually weaned off drips, extubated, and started on feeds. Discussion Electrical injury, specifically lightning injury is an uncommon but devastating cause of injury in pediatric patients. This patient with suspected abusive use of a dog shock collar presented similar to a lightning strike. Common entrance points include the hands and head, similar to our patient with linear wounds on his forehead. When current enters, it passes through tissues with the least resistance. Nerves, blood vessels, and muscles, have high fluid and electrolyte content and are commonly affected. Exit points are extremities: our child who had circumferential burns around his arm creases and ankles. Linear burns preferentially follow areas of high sweat concentration, and are thought to be due to vaporization of water on the skin’s surface. The most common cause of death from a lightning strike is due to cardiopulmonary arrest. The massive depolarization of the myocardium can result in arrhythmias and myocardial necrosis. The patient presented in cardiogenic shock with evident cardiac damage. Electricity going through vessels can lead to vaporization of intravascular water. This can explain his severe hypernatremia. He also sustained other internal organ injuries (adrenal glands, pancreas, liver, and kidney). Electrical discharge also leads to direct skeletal muscle injury in addition to prolonged muscular spasm. Rhabdomyolysis, the acute damage of muscle, leads to release of potentially toxic components into the circulation which could lead to acute renal failure. The patient had severe rhabdomyolysis and renal injury. Early hypocalcemia has been consistently demonstrated in patients with rhabdomyolysis. This was present in the patient and led to increased vasopressor needs. Central nervous system injuries are also common which can include encephalopathy, hypoxic injury, and cerebral infarction. The patient had evidence of brain injury as seen on MRI. Conclusion Electrical injuries due to lightning strikes and abusive use of a dog shock collar are rare, but can both present in similar ways with respiratory failure, shock, hypernatremia, rhabdomyolysis, brain injury, and multiorgan damage. Although rare, it is essential for early identification and prompt management for acute and chronic complications in these children.

Keywords: cardiogenic shock, dog shock collar, lightning strike, rhabdomyolysis

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2624 Autonomic Nervous System Changes Associated with Rheumatoid Arthritis: Clinical and Electrophysiological Study

Authors: Emmanuel Kamal Aziz Saba, Hussein Al-Moghazy Sultan

Abstract:

The aim of this study was to evaluate clinically and electro physiologically the autonomic nervous system changes associated with rheumatoid arthritis (RA). The present study included 25 patients with RA [22 women (88%)] and 30 apparently healthy control subjects [27 women (90%)]. A thorough clinical examination was carried out. Disease activity and functional disability were assessed. Tests for assessment of autonomic functions include active and passive orthostatic stress tests, and sympathetic skin response (SSR). The presence of abnormality in 2 tests or more was a clue for the presence of autonomic neuropathy (AN). Sural sensory nerve conduction study and posterior tibial motor nerve conduction study were done. There was a statistically significant decrease in standing systolic and diastolic blood pressure (BP) components of the active orthostatic stress test and SSR amplitude as well as statistically significant prolongation of SSR latency of RA patients when compared to control. Three patients (12%) had clinical symptoms suggestive of AN; increased to 14 patients (56 %) when orthostatic stress tests and SSR were utilized. There were no statistically significant differences between patients with different disease activity score 28 with 4 variables grades of RA activity and SSR latency and amplitude. There were no statistically significant differences between patients with different Stanford Health Assessment Questionnaire Disability Index grades of RA functional disability and SSR latency and amplitude. In conclusion, autonomic neuropathy is a common extra-articular manifestation of RA affecting sympathetic and parasympathetic fibers.

Keywords: autonomic neuropathy, orthostatic stress test, rheumatoid arthritis, sympathetic skin response

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2623 The International Classification of Functioning, Disability and Health (ICF) as a Problem-Solving Tool in Disability Rehabilitation and Education Alliance in Metabolic Disorders (DREAM) at Sultan Bin Abdul Aziz Humanitarian City:A Prototype for Reh

Authors: Hamzeh Awad

Abstract:

Disability is considered to be a worldwide complex phenomenon which rising at a phenomenal rate and caused by many different factors. Chronic diseases such as cardiovascular disease and diabetes can lead to mobility disability in particular and disability in general. The ICF is an integrative bio-psycho-social model of functioning and disability and considered by the World Health Organization (WHO) to be a reference for disability classification using its categories and core set to classify disorder’s functional limitations. Specialist programs at Sultan Bin Abdul Aziz Humanitarian City (SBAHC) are providing both inpatient and outpatient services have started to implement the ICF and use it as a problem solving tool in Rehab. Diabetes is leading contributing factor for disability and considered epidemic in several Gulf countries including the Kingdom of Saudi Arabia (KSA), where its prevalence continues to increase dramatically. Metabolic disorders, mainly diabetes are not well covered in Rehab field. The purpose of this study is present to research and clinical rehabilitation field of DREAM and ICF as a framework in clinical and research setting in Rehab service. Also, shed the light on using the ICF as problem solving tool at SBAHC. There are synergies between disability causes and wider public health priorities in relation to both chronic disease and disability prevention. Therefore, there is a need for strong advocacy and understanding of the role of ICF as a reference in Rehab settings in Middle East if we wish to seize the opportunity to reverse current trends of acquired disability in the region.

Keywords: international classification of functioning, disability and health (ICF), prototype, rehabilitation and diabetes

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2622 Traditional Medicine and Islamic Holistic Approach in Palliative Care Management of Terminal Illpatient of Cancer

Authors: Mohammed Khalil Ur Rahman, Mohammed Alsharon, Arshad Muktar, Zahid Shaik

Abstract:

Any ailment can go into terminal stages, cancer being one such disease which is many times detected in latent stages. Cancer is often characterized by constitutional symptoms which are agonizing in nature which disturbs patients and their family as well. In order to relieve such intolerable symptoms treatment modality employed is known to be ‘Palliative Care’. The goal of palliative care is to enhance patient’s quality of life by relieving or rather reducing the distressing symptoms of patients such as pain, nausea/ vomiting, anorexia/loss of appetite, excessive salivation, mouth ulcers, weight loss, constipation, oral thrush, emaciation etc. which are due to the effect of disease or due to the undergoing treatment such as chemotherapy, radiation etc. Ayurveda and Unani as well as other traditional medicines is getting more and more international attention in recent years and Ayurveda and Unani holistic perspective of the disease, it seems that there are many herbs and herbomineral preparation which can be employed in the treatment of malignancy and also in palliative care. Though many of them have yet to be scientifically proved as anti-cancerous but there is definitely a positive lead that some of these medications relieve the agonising symptoms thereby making life of the patient easy. Health is viewed in Islam in a holistic way. One of the names of the Quran is al-shifa' meaning ‘that which heals’ or ‘the restorer of health’ to refer to spiritual, intellectual, psychological, and physical health. The general aim of medical science, according to Islam, is to secure and adopt suitable measures which, with Allah’s permission, help to preserve or restore the health of the human body. Islam motivates the Physician to view the patient as one organism. The patient has physical, social, psychological, and spiritual dimensions that must be considered in synthesis with an integrated, holistic approach. Aims & Objectives: - To suggest herbs which are mentioned in Ayurveda Unani with potential palliative activity in case of Cancer patients. - Most of tibb nabawi [Prophetic Medicine] is preventive medicine and must have been divinely inspired. - Spiritual Aspects of Healing: Prayer, dua, recitation of the Quran - Remembrance of Allah play a central role.Materials & Method: Literary review of the herbs supported with experiential evidence will be discussed. Discussion: On the basis of collected data subject will be discussed in length. Conclusion: Will be presented in paper.

Keywords: palliative care, holistic, Ayurvedic and Unani traditional system of medicine, Quran, hadith

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2621 Transcriptional Differences in B cell Subpopulations over the Course of Preclinical Autoimmunity Development

Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

Abstract:

Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

Keywords:

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2620 Hemodialysis Technique in a Diabetic Population

Authors: Daniel Thompson, Sophie Cerutti, Muhammad Peerbux, Hansraj Bookun

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Introduction: Diabetic nephropathy is the leading cause end stage renal failure in Australia, responsible for 36% of cases. Patients who require dialysis may be suitable for haemodialysis through an arteriovenous fistula (AVF), and preoperatively careful planning is required to select suitable vessels for a long-lasting fistula that provides suitable dialysis access. Due to high levels of vascular disease in diabetic patients, we sought to investigate whether there is a difference in the types of autologous AVFs created for diabetic patients in renal failure compared to their non-diabetic counterparts. Method: Data was collected from the Australasian Vascular Audit, for all vascular surgery completed at St. Vincent’s Hospital Melbourne between 2011-2020. Patients were selected by operative type, creation of AVF, and compared in two groups, diabetic patients and patients without diabetes. Chi-squared test was utilised to determine significance. Results: Data analysis is ongoing and will be complete with updated abstract in time for the conference. Discussion: Diabetic nephropathy is the cause for roughly a third of end stage renal failure in Australia. Diabetic patients present with a unique set of challenges when it comes to dialysis access due to increased risk of peripheral vascular disease and arterial calcification. Care must be taken in the creation of fistulas to minimise complications and increase the chance of long-lasting access. Our study investigates the difference in autologous AVFs between diabetics and non-diabetics, and results may be used to influence location of fistula creation. Further research may be used to investigate patency rates of fistulas in diabetics vs non-diabetics which would further influence treatment decisions.

Keywords: dialysis, diabetes, renal access, fistula

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2619 Abdominal Organ Segmentation in CT Images Based On Watershed Transform and Mosaic Image

Authors: Belgherbi Aicha, Hadjidj Ismahen, Bessaid Abdelhafid

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Accurate Liver, spleen and kidneys segmentation in abdominal CT images is one of the most important steps for computer aided abdominal organs pathology diagnosis. In this paper, we have proposed a new semi-automatic algorithm for Liver, spleen and kidneys area extraction in abdominal CT images. Our proposed method is based on hierarchical segmentation and watershed algorithm. In our approach, a powerful technique has been designed to suppress over-segmentation based on mosaic image and on the computation of the watershed transform. The algorithm is currency in two parts. In the first, we seek to improve the quality of the gradient-mosaic image. In this step, we propose a method for improving the gradient-mosaic image by applying the anisotropic diffusion filter followed by the morphological filters. Thereafter we proceed to the hierarchical segmentation of the liver, spleen and kidney. To validate the segmentation technique proposed, we have tested it on several images. Our segmentation approach is evaluated by comparing our results with the manual segmentation performed by an expert. The experimental results are described in the last part of this work.

Keywords: anisotropic diffusion filter, CT images, morphological filter, mosaic image, multi-abdominal organ segmentation, mosaic image, the watershed algorithm

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2618 Bulbar Conjunctival Kaposi's Sarcoma Unmasked by Immune Reconstitution Syndrome

Authors: S. Mohd Afzal, R. O'Connell

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Kaposi's sarcoma (KS) is the most common HIV-related cancer, and ocular manifestations constitute at least 25% of all KS cases. However, ocular presentations often occur in the context of systemic KS, and isolated lesions are rare. We report a unique case of ocular KS masquerading as subconjunctival haemorrhage, and only developing systemic manifestations after initiation of HIV treatment. Case: A 49-year old man with previous hypertensive stroke and newly diagnosed HIV infection presented with an acutely red left eye following repeated bouts of coughing. Given the convincing history of poorly controlled hypertension and cough, a diagnosis of subconjunctival haemorrhage was made. Over the next week, his ocular lesion began to improve and he subsequently started anti-retroviral therapy. Prior to receiving anti-retroviral therapy, his CD4+ lymphocyte count was 194 cells/mm3 with HIV viral load greater than 1 million/ml. This rapidly improved to a viral load of 150 copies/ml within 2 weeks of starting treatment. However, a few days after starting HIV treatment, his ocular lesion recurred. Ophthalmic examination was otherwise normal. He also developed widespread lymphadenopathy and multiple dark lesions on his torso. Histology and virology confirmed KS, systemically triggered by Immune Reconstitution Syndrome (KS-IRIS). The patient has since undergone chemotherapy successfully. Discussion: Kaposi's sarcoma is an atypical tumour caused by human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). In immunosuppressed patients, KSHV can also cause lymphoproliferative disorders such as primary effusion lymphoma and Castleman's disease (in our patient’s case, this was excluded through histological analysis of lymph nodes). KSHV is one of the seven currently known human oncoviruses, and its pathogenesis is poorly understood. Up to 13% of patients with HIV-related KS experience worsening of the disease after starting anti-retroviral treatment, due to a sudden increase in CD4 cell counts. Histology remains the diagnostic gold standard. Current British HIV Association (BHIVA) guidelines recommend treatment using anti-retroviral drugs, with either intralesional vinblastine for local disease or systemic chemotherapy for disseminated KS. Conclusion: This case is unique as ocular KS as initial presentation is rare and our patient's diagnosis was only made after systemic lesions were triggered by immune reconstitution. KS should be considered as an important differential diagnosis for red eyes in all patients at risk of acquiring HIV infection.

Keywords: human herpesvirus 8, human immunodeficiency virus, immune reconstitution syndrome, Kaposi’s sarcoma, Kaposi’s sarcoma-associated herpesvirus

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