Search results for: pancreatic injury
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 931

Search results for: pancreatic injury

811 Rethinking the Value of Pancreatic Cyst CEA Levels from Endoscopic Ultrasound Fine-Needle Aspiration (EUS-FNA): A Longitudinal Analysis

Authors: Giselle Tran, Ralitza Parina, Phuong T. Nguyen

Abstract:

Background/Aims: Pancreatic cysts (PC) have recently become an increasingly common entity, often diagnosed as incidental findings on cross-sectional imaging. Clinically, management of the lesions is difficult because of uncertainties in their potential for malignant degeneration. Prior series have reported that carcinoembryonic antigen (CEA), a biomarker collected from cyst fluid aspiration, has a high diagnostic accuracy for discriminating between mucinous and non-mucinous lesions, at the patient’s initial presentation. To the author’s best knowledge, no prior studies have reported PC CEA levels obtained from endoscopic ultrasound fine-needle aspiration (EUS-FNA) over years of serial EUS surveillance imaging. Methods: We report a consecutive retrospective series of 624 patients who underwent EUS evaluation for a PC between 11/20/2009 and 11/13/2018. Of these patients, 401 patients had CEA values obtained at the point of entry. Of these, 157 patients had two or more CEA values obtained over the course of their EUS surveillance. Of the 157 patients (96 F, 61 M; mean age 68 [range, 62-76]), the mean interval of EUS follow-up was 29.7 months [3.5-128]. The mean number of EUS procedures was 3 [2-7]. To assess CEA value fluctuations, we defined an appreciable increase in CEA as "spikes" – two-times increase in CEA on a subsequent EUS-FNA of the same cyst, with the second CEA value being greater than 1000 ng/mL. Using this definition, cysts with a spike in CEA were compared to those without a spike in a bivariate analysis to determine if a CEA spike is associated with poorer outcomes and the presence of high-risk features. Results: Of the 157 patients analyzed, 29 had a spike in CEA. Of these 29 patients, 5 had a cyst with size increase >0.5cm (p=0.93); 2 had a large cyst, >3cm (p=0.77); 1 had a cyst that developed a new solid component (p=0.03); 7 had a cyst with a solid component at any time during surveillance (p=0.08); 21 had a complex cyst (p=0.34); 4 had a cyst categorized as "Statistically Higher Risk" based on molecular analysis (p=0.11); and 0 underwent surgical resection (p=0.28). Conclusion: With serial EUS imaging in the surveillance of PC, an increase in CEA level defined as a spike did not predict poorer outcomes. Most notably, a spike in CEA did not correlate with the number of patients sent to surgery or patients with an appreciable increase in cyst size. A spike in CEA did not correlate with the development of a solid nodule within the PC nor progression on molecular analysis. Future studies should focus on the selected use of CEA analysis when patients undergo EUS surveillance evaluation for PCs.

Keywords: carcinoembryonic antigen (CEA), endoscopic ultrasound (EUS), fine-needle aspiration (FNA), pancreatic cyst, spike

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810 Computational Study on Traumatic Brain Injury Using Magnetic Resonance Imaging-Based 3D Viscoelastic Model

Authors: Tanu Khanuja, Harikrishnan N. Unni

Abstract:

Head is the most vulnerable part of human body and may cause severe life threatening injuries. As the in vivo brain response cannot be recorded during injury, computational investigation of the head model could be really helpful to understand the injury mechanism. Majority of the physical damage to living tissues are caused by relative motion within the tissue due to tensile and shearing structural failures. The present Finite Element study focuses on investigating intracranial pressure and stress/strain distributions resulting from impact loads on various sites of human head. This is performed by the development of the 3D model of a human head with major segments like cerebrum, cerebellum, brain stem, CSF (cerebrospinal fluid), and skull from patient specific MRI (magnetic resonance imaging). The semi-automatic segmentation of head is performed using AMIRA software to extract finer grooves of the brain. To maintain the accuracy high number of mesh elements are required followed by high computational time. Therefore, the mesh optimization has also been performed using tetrahedral elements. In addition, model validation with experimental literature is performed as well. Hard tissues like skull is modeled as elastic whereas soft tissues like brain is modeled with viscoelastic prony series material model. This paper intends to obtain insights into the severity of brain injury by analyzing impacts on frontal, top, back, and temporal sites of the head. Yield stress (based on von Mises stress criterion for tissues) and intracranial pressure distribution due to impact on different sites (frontal, parietal, etc.) are compared and the extent of damage to cerebral tissues is discussed in detail. This paper finds that how the back impact is more injurious to overall head than the other. The present work would be helpful to understand the injury mechanism of traumatic brain injury more effectively.

Keywords: dynamic impact analysis, finite element analysis, intracranial pressure, MRI, traumatic brain injury, von Misses stress

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809 Application of the Tripartite Model to the Link between Non-Suicidal Self-Injury and Suicidal Risk

Authors: Ashley Wei-Ting Wang, Wen-Yau Hsu

Abstract:

Objectives: The current study applies and expands the Tripartite Model to elaborate the link between non-suicidal self-injury (NSSI) and suicidal behavior. We propose a structural model of NSSI and suicidal risk, in which negative affect (NA) predicts both anxiety and depression, positive affect (PA) predicts depression only, anxiety is linked to NSSI, and depression is linked to suicidal risk. Method: Four hundreds and eighty seven undergraduates participated. Data were collected by administering self-report questionnaires. We performed hierarchical regression and structural equation modeling to test the proposed structural model. Results: The results largely support the proposed structural model, with one exception: anxiety was strongly associated with NSSI and to a lesser extent with suicidal risk. Conclusions: We conclude that the co-occurrence of NSSI and suicidal risk is due to NA and anxiety, and suicidal risk can be differentiated by depression. Further theoretical and practical implications are discussed.

Keywords: non-suicidal self-injury, suicidal risk, anxiety, depression, the tripartite model, hierarchical relationship

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808 Efficacy of Sea Water with Reduced Rate Herbicide to Control Weeds in Tropical Turf

Authors: Md. Kamal Uddin, Abdul Shukor Juraimi, Md. Parvez Anwar

Abstract:

Seawater with reduced herbicide could be considered as a low cost environment friendly alternative method for weed control in turfgrass. Different concentration of sea water in combination with trifloxysulfuron-sodium and quinclorac were used to determine weed control level in turfgrass field. The weed species S. diander, C. aromaticus, and C. rotundus except E. atrovirens were fully controlled when treated with ¾ recommended trifloxysulfuron–sodium with sea water, ¾ recommended trifloxysulfuron–sodium with ¾ sea water, ½ recommended trifloxysulfuron–sodium with sea water, ¾ recommended quinclorac with sea water and ¾ recommended quinclorac with ¾ sea water. Eragrostis atrovirens showed maximum 48% injury when treated with ¾ recommended trifloxysulfuron–sodium and sea water. Among the tested turf grasses, P. vaginatum showed only 8% injury to sea water in combination with ¾ recommended quinclorac, indicating greater salt tolerance. Zoysia japonica also showed no more than 14% injury when treated with sea water in combination with ¾ recommended trifloxysulfuron–sodium or quinclorac.

Keywords: sea water, trifloxysulfuron–sodium, quinclorac, turf

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807 Developing a South African Model of Neuropsychological Rehabilitation for Adults After Acquired Brain Injury

Authors: Noorjehan Joosub-Vawda

Abstract:

Objectives: The aim of this poster presentation is to examine cultural contextual understandings of ABI that could aid conceptualisation and the development of a model for neuropsychological rehabilitation in this context. Characteristics of the South African context that make the implementation of international NR practices difficult include socioeconomic disparities, sociocultural influences, lack of accessibility to healthcare services, and poverty and unemployment levels. NR services in the developed world have characteristics such as low staff-to-patient ratios and interdisciplinary teams that make them unsuitable for the resource-constrained South African context. Methods: An exploratory, descriptive research design based on programme theory is being followed in the development of a South African model of neuropsychological rehabilitation. Results: The incorporation of African traditional understandings and practices, such as beliefs about ancestral spirits in the etiology of Acquired Brain Injury are relevant to the planning of rehabilitation interventions. Community-Based Rehabilitation workers, psychoeducation, and cooperation among the different systemic levels especially in rural settings is also needed to improve services offered to patients living with ABI. Conclusions. The preliminary model demonstrated in this poster will attempt to build on the strengths of South African communities, incorporating valuable evidence from international models to serve those affected with brain injury in this context.

Keywords: neuropsychological rehabilitation, South Africa, acquired brain injury, developing context

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806 Utility of Thromboelastography to Reduce Coagulation-Related Mortality and Blood Component Rate in Neurosurgery ICU

Authors: Renu Saini, Deepak Agrawal

Abstract:

Background: Patients with head and spinal cord injury frequently have deranged coagulation profiles and require blood products transfusion perioperatively. Thromboelastography (TEG) is a ‘bedside’ global test of coagulation which may have role in deciding the need of transfusion in such patients. Aim: To assess the usefulness of TEG in department of neurosurgery in decreasing transfusion rates and coagulation-related mortality in traumatic head and spinal cord injury. Method and Methodology: A retrospective comparative study was carried out in the department of neurosurgery over a period of 1 year. There are two groups in this study. ‘Control’ group constitutes the patients in whom data was collected over 6 months (1/6/2009-31/12/2009) prior to installation of TEG machine. ‘Test’ group includes patients in whom data was collected over 6months (1/1/2013-30/6/2013) post TEG installation. Total no. of platelet, FFP, and cryoprecipitate transfusions were noted in both groups along with in hospital mortality and length of stay. Result: Both groups were matched in age and sex of patients, number of head and spinal cord injury cases, number of patients with thrombocytopenia and number of patients who underwent operation. Total 178 patients (135 head injury and 43 spinal cord injury patents) were admitted in neurosurgery department during time period June 2009 to December 2009 i.e. prior to TEG installation and after TEG installation a total of 243 patients(197 head injury and 46 spinal cord injury patents) were admitted. After TEG introduction platelet transfusion significantly reduced (p=0.000) compare to control group (67 units to 34 units). Mortality rate was found significantly reduced after installation (77 patients to 57 patients, P=0.000). Length of stay was reduced significantly (Prior installation 1-211days and after installation 1-115days, p=0.02). Conclusion: Bedside TEG can dramatically reduce platelet transfusion components requirement in department of neurosurgery. TEG also lead to a drastic decrease in mortality rate and length of stay in patients with traumatic head and spinal cord injuries. We recommend its use as a standard of care in the patients with traumatic head and spinal cord injuries.

Keywords: blood component transfusion, mortality, neurosurgery ICU, thromboelastography

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805 The Severity of Electric Bicycle Injuries Compared to Classic Bicycle Injuries in Children: A Retrospective Review

Authors: Tali Capua, Karin Hermon, Miguel Glatstein, Oren Tavor, Ayelet Rimon

Abstract:

Background: Electric bicycles (E-bikes) are one of a wide range of light electric vehicles that provide convenient local transportation and attractive recreational opportunities. Along with their growing use worldwide, the E-bike related injury rate increases. To the best of our knowledge, this study is the first to specifically compare E-bike with classic bicycle related injuries in children. Methods: Data of all pediatric ( < 16 years of age) bicycle related injuries presenting to an urban level I trauma center between 2014 and 2015 were collected and analyzed. The recorded data included age, gender, details of the accident, as well severity of injury, medical diagnosis, and the outcome. Abbreviated Injury Score (AIS) and Injury Severity Score (ISS) were calculated for each patient. Data of E-bike related injuries and classic bicycle were then compared. Results: A total of 124 bicycle related injuries and 97 E-bike related injuries presented to the emergency department. Once pedestrians and bicycle passengers were removed, the groups of riders consisted of 111 bikers and 85 E-bikers. The mean age of bikers was 9.9 years (range 3-16 years) and of E-bikers was 13.7 years (range 7.5-16 years). Injuries to the head and the extremities were common in both groups. Compared to bikers, E-bikers had significantly more injuries to intra-abdominal organs (p = 0.04). Twenty patients (16%) with bicycle related injuries were admitted, and 13 (15%) patients with E-bike related injuries, of the latter group four underwent surgical intervention. ISS scores were low overall, but the injuries of higher severity (ISS > 9) were among the E-bikers. Conclusions: This study provides unique information which suggests that injuries in E-bikers tend to be more severe than in classic bikers. There is a need for regulation regarding the use of E-bikes to enhance the safety of both bikers and other road and pavement users.

Keywords: bicycle, electric bicycle, injury, pediatric, trauma

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804 Modelling the Effect of Physical Environment Factors on Child Pedestrian Severity Collisions in Malaysia: A Multinomial Logistic Regression Analysis

Authors: Muhamad N. Borhan, Nur S. Darus, Siti Z. Ishak, Rozmi Ismail, Siti F. M. Razali

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Children are at the greater risk to be involved in road traffic collisions due to the complex interaction of various elements in our transportation system. It encompasses interactions between the elements of children and driver behavior along with physical and social environment factors. The present study examined the effect between the collisions severity and physical environment factors on child pedestrian collisions. The severity of collisions is categorized into four injury outcomes: fatal, serious injury, slight injury, and damage. The sample size comprised of 2487 cases of child pedestrian-vehicle collisions in which children aged 7 to 12 years old was involved in Malaysia for the years 2006-2015. A multinomial logistic regression was applied to establish the effect between severity levels and physical environment factors. The results showed that eight contributing factors influence the probability of an injury road surface material, traffic system, road marking, control type, lighting condition, type of location, land use and road surface condition. Understanding the effect of physical environment factors may contribute to the improvement of physical environment design and decrease the collision involvement.

Keywords: child pedestrian, collisions, primary school, road injuries

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803 Neuroprotective Effects of Allium Cepa Extract Against Ischemia Reperfusion Induced Cognitive Dysfunction and Brain Damage in Mice

Authors: Jaspal Rana

Abstract:

Oxidative stress has been identified as an underlying cause of ischemia-reperfusion (IR) related cognitive dysfunction and brain damage. Therefore, antioxidant based therapies to treat IR injury are being investigated. Allium cepa L. (onion) is used as culinary medicine and is documented to have marked antioxidant effects. Hence, the present study was designed to evaluate the effect of A. cepa outer scale extract (ACE) against IR induced cognition and biochemical deficit in mice. ACE was prepared by maceration with 70% methanol and fractionated into ethylacetate and aqueous fractions. Bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion was used to induce cerebral IR injury. Following IR injury, ACE (100 and 200 mg/kg) was administered orally to animals for 7 days once daily. Behavioral outcomes (memory and sensorimotor functions) were evaluated using Morris water maze and neurological severity score. Cerebral infarct size, brain thiobarbituric acid reactive species, reduced glutathione, and superoxide dismutase activity was also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rise in brain oxidative stress in animals. The results of the present investigation revealed that ACE improved functional outcomes after cerebral IR injury which may be attributed to its antioxidant properties.

Keywords: ischemia-reperfusion, neuroprotective, stroke, antioxidant

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802 Detection Kit of Type 1 Diabetes Mellitus with Autoimmune Marker GAD65 (Glutamic Acid Decarboxylase)

Authors: Aulanni’am Aulanni’am

Abstract:

Incidence of Diabetes Mellitus (DM) progressively increasing it became a serious problem in Indonesia and it is a disease that government is priority to be addressed. The longer a person is suffering from diabetes the more likely to develop complications particularly diabetic patients who are not well maintained. Therefore, Incidence of Diabetes Mellitus needs to be done in the early diagnosis of pre-phase of the disease. In this pre-phase disease, already happening destruction of pancreatic beta cells and declining in beta cell function and the sign autoimmunity reactions associated with beta cell destruction. Type 1 DM is a multifactorial disease triggered by genetic and environmental factors, which leads to the destruction of pancreatic beta cells. Early marker of "beta cell autoreactivity" is the synthesis of autoantibodies against 65-kDa protein, which can be a molecule that can be detected early in the disease pathomechanism. The importance of early diagnosis of diabetic patients held in the phase of pre-disease is to determine the progression towards the onset of pancreatic beta cell destruction and take precautions. However, the price for this examination is very expensive ($ 150/ test), the anti-GAD65 abs examination cannot be carried out routinely in most or even in all laboratories in Indonesia. Therefore, production-based Rapid Test Recombinant Human Protein GAD65 with "Reverse Flow Immunchromatography Technique" in Indonesia is believed to reduce costs and improve the quality of care of patients with diabetes in Indonesia. Rapid Test Product innovation is very simple and suitable for screening and routine inspection of GAD65 autoantibodies. In the blood serum of patients with diabetes caused by autoimmunity, autoantibody-GAD65 is a major serologic marker to detect autoimmune reaction because their concentration level of stability.GAD65 autoantibodies can be found 10 years before clinical symptoms of diabetes. Early diagnosis is more focused to detect the presence autontibodi-GAD65 given specification and high sensitivity. Autoantibodies- GAD65 that circulates in the blood is a major indicator of the destruction of the islet cells of the pancreas. Results of research in collaboration with Biofarma has produced GAD65 autoantibodies based Rapid Test had conducted the soft launch of products and has been tested with the results of a sensitivity of 100 percent and a specificity between 90 and 96% compared with the gold standard (import product) which worked based on ELISA method.

Keywords: diabetes mellitus, GAD65 autoantibodies, rapid test, sensitivity, specificity

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801 Outcome of Bowel Management Program in Patient with Spinal Cord Injury

Authors: Roongtiwa Chobchuen, Angkana Srikhan, Pattra Wattanapan

Abstract:

Background: Neurogenic bowel is common condition after spinal cord injury. Most of spinal cord injured patients have motor weakness, mobility impairment which leads to constipation. Moreover, the neural pathway involving bowel function is interrupted. Therefore, the bowel management program should be implemented in nursing care in the earliest time after the onset of the disease to prevent the morbidity and mortality. Objective: To study the outcome of bowel management program of the patients with spinal cord injury who admitted for rehabilitation program. Study design: Descriptive study. Setting: Rehabilitation ward in Srinagarind Hospital. Populations: patients with subacute to chronic spinal cord injury who admitted at rehabilitation ward, Srinagarind hospital, aged over 18 years old. Instrument: The neurogenic bowel dysfunction score (NBDS) was used to determine the severity of neurogenic bowel. Procedure and statistical analysis: All participants were asked to complete the demographic data; age gender, duration of disease, diagnosis. The individual bowel function was assessed using NBDS at admission. The patients and caregivers were trained by nurses about the bowel management program which consisted of diet modification, abdominal massage, digital stimulation, stool evacuation including medication and physical activity. The outcome of the bowel management program was assessed by NBDS at discharge. The chi-square test was used to detect the difference in severity of neurogenic bowel at admission and discharge. Results: Sixteen spinal cord injured patients were enrolled in the study (age 45 ± 17 years old, 69% were male). Most of them (50%) were tetraplegia. On the admission, 12.5%, 12.5%, 43.75% and 31.25% were categorized as very minor (NBDS 0-6), minor (NBDS 7-9), moderate (NBDS 10-13) and severe (NBDS 14+) respectively. The severity of neurogenic bowel was decreased significantly at discharge (56.25%, 18.755%, 18.75% and 6.25% for very minor, minor, moderate and severe group respectively; p < 0.001) compared with NBDS at admission. Conclusions: Implementation of the effective bowel program decrease the severity of the neurogenic bowel in patient with spinal cord injury.

Keywords: neurogenic bowel, NBDS, spinal cord injury, bowel program

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800 The Relation Between Oxidative Stress, Inflammation, and Neopterin in the Paraquat-Induced Lung Toxicity

Authors: M. Toygar, I. Aydin, M. Agilli, F. N. Aydin, M. Oztosun, H. Gul, E. Macit, Y. Karslioglu, T. Topal, B. Uysal, M. Honca

Abstract:

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon g and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1 (TGF-1) levels were significantly higher than the sham group (in all, p< 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p 1/4 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1 levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Keywords: paraquat, inflammation, oxidative stress, neopterin, lung toxicity

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799 Retrospective Data Analysis of Penetrating Injuries Admitted to Jigme Dorji Wangchuck National Referral Hospital (JDWNRH), Thimphu, Bhutan, Due to Traditional Sports over a Period of 3 Years

Authors: Sonam Kelzang

Abstract:

Background: Penetrating injuries as a result of traditional sports (Archery and Khuru) are commonly seen in Bhutan. To our knowledge, there is no study carried out looking into the data of penetrating injuries due to traditional sports. Aim: This is a retrospective analysis of cases of penetrating injuries as a result of traditional sports admitted to JDWNRH over the last 3 years to draw an inference on the pattern of injury and associated morbidity and mortality. Method: Data on penetrating injuries related to traditional sports (Archery and Khuru) were collected and reviewed over the period of 3 years. Assault cases were excluded. For each year we analysed age, sex, parts of the body affected, agent of injury and whether admission was required or not. Results: Out of the total 44 victims of penetrating injury by traditional sports (Archery and Khuru) between 2013 and 2015 (average of 15 cases of penetrating injuries per year). Eighty-five percent were male and 15% were female. Their age ranged from 4 yrs to 62 years. Sixty-one percent of the victims were in the working age group of 19-58 years; 30% of the victims were referred from various district hospitals; 38% of the victims needed admission; 42 % of the victims suffered injury to the head; and 54% of the injuries were caused by Khuru. Conclusion: Penetrating injuries due to traditional sports admitted to JDWNRH, Thimphu, remained same over the three years period despite safety regulations in place. Although there were no deaths during the last three years, morbidity still remains high.

Keywords: archery, Bhutan, Khuru, darts

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798 Relationship between Pain, Social Support and Socio-Economic Indicators in Individuals with Spinal Cord Injury

Authors: Zahra Khazaeipour, Ehsan Ahmadipour, Vafa Rahimi-Movaghar, Fereshteh Ahmadipour

Abstract:

Research Objectives: Chronic pain is one of the common problems associated with spinal cord injuries (SCI), which causes many complications. Therefore, this study intended to evaluate the relationship between pain and demographic, injury characteristics, socio-economic and social support in individuals with spinal cord Injury in Iran. Design: Descriptive cross-sectional study. Setting: Brain and Spinal Cord Injury Research Center (BASIR), Tehran University of Medical Sciences, Tehran, Iran, between 2012 and 2013. Participants: The participants were 140 individuals with SCI, 101 (72%) men and 39 (28%) women, with mean age of 29.4 ±7.9 years. Main Outcome Measure: The Persian version of the Brief Pain Inventory (BPI) was used to measure the pain, and the Multidimensional Scale of Perceived Social Support (MSPSS) was used to measure social support. Results: About 50.7% complained about having pain, which 79.3% had bilateral pain. The most common locations of pain were lower limbs and back. The most quality of pain was described as aching (41.4%), and tingling (32.9%). Patients with a medium level of education had the least pain compared to high and low level of education. SCI individuals with good economic situation reported higher frequency of having pain. There was no significant relationship between pain and social support. There was positive correlation between pain and impairment of mood, normal work, relations with other people and lack of sleep (P < 0.001). Conclusion: These findings revealed the importance of socioeconomic factors such as economic situation and educational level in understanding chronic pain in people with SCI and provide further support for the bio-psychosocial model. Hence, multidisciplinary evaluations and treatment strategies are advocated, including biomedical, psychological, and psycho-social interventions.

Keywords: pain, social support, socio-economic indicators, spinal cord injury

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797 The Impact of Psychiatric Symptoms on Return to Work after Occupational Injury

Authors: Kuan-Han Lin, Kuan-Yin Lin, Ka-Chun Siu

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The purpose of this systematic review was to determine the impact of post-traumatic stress disorders (PTSD) symptom or depressive symptoms on return to work (RTW) after occupational injury. The original articles of clinical trials and observational studies from PubMed, MEDLINE, and PsycINFO between January 1980 and November 2016 were retrieved. Two reviewers evaluated the abstracts identified by the search criteria for full-text review. To be included in the final analysis, studies were required to use either intervention or observational study design to examine the association between psychiatric symptoms and RTW. A modified checklist designed by Downs & Black and Crombie was used to assess the methodological quality of included study. A total of 58 articles were identified from the electronic databases after duplicate removed. Seven studies fulfilled the inclusion criteria and were critically reviewed. The rates of RTW in the included studies were reported to be 6% to 63.6% among workers after occupational injuries. This review found that post-traumatic stress symptom and depressive symptoms were negatively associated with RTW. Although the impact of psychiatric symptoms on RTW after occupational injury remains poorly understood, this review brought up the important information that injured workers with psychiatric symptoms had poor RTW outcome. Future work should address the effective management of psychiatric factors affecting RTW among workers.

Keywords: depressive symptom, occupational injury, post-traumatic stress disorder, return to work

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796 Predictors of Recent Work-Related Injury in a Rapidly Developing Country: Results from a Worker Survey in Qatar

Authors: Ruben Peralta, Sam Thomas, Nazia Hirani, Ayman El-Menyar, Hassan Al-Thani, Mohammed Al-Thani, Mohammed Al-Hajjaj, Rafael Consunji

Abstract:

Moderate to severe work-related injuries [WRI's] are a leading cause of trauma admission in Qatar but information on risk factors for their incidence are lacking. This study aims to document and analyze the predictive characteristics for WRI to inform the creation of targeted interventions to improve worker safety in Qatar. This study was conducted as part of the NPRP grant # 7 - 1120 - 3 - 288, titled "A Unified Registry for Occupational Injury Prevention in Qatar”. 266 workers were interviewed using a standard questionnaire, during ‘World Day for Safety and Health at Work’, a Ministry of Public Health event, none refused interview. Nurses and doctors from the Hamad Trauma Center conducted the interviews. Questions were translated into the worker’s native language when it was deemed necessary. Standard information on epidemiologic characteristics and incidence of work-related injury were collected and compared between nationalities and those injured versus those not injured. 262 males and 4 females were interviewed. 17 [6.4%] reported a WRI in the last 24 months. More than half of the injured worked in construction [59%] followed by water supply [11.8%]. Factors significantly associated with recent injury were: Working for a company with > 500 employees and speaking Hindi. Protective characteristics included: Being from the Philippines or Sri Lanka, speaking Arabic, working in healthcare, an office or trading and company size between 100-500 employees. Years of schooling and working in Qatar were not predictive factor for WRI. The findings from this survey should guide future research that will better define worker populations at an increased risk for WRI and inform recruiters and sending countries. A focus on worker language skills, interventions in the construction industry and occupational safety in large companies is needed.

Keywords: occupational injury, prevention, safety, trauma, work related injury

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795 Antioxidant Mediated Neuroprotective Effects of Allium Cepa Extract Against Ischemia Reperfusion Induced Cognitive Dysfunction and Brain Damage in Mice

Authors: Jaspal Rana, Varinder Singh

Abstract:

Oxidative stress has been identified as an underlying cause of ischemia-reperfusion (IR) related cognitive dysfunction and brain damage. Therefore, antioxidant based therapies to treat IR injury are being investigated. Allium cepa L. (onion) is used as culinary medicine and is documented to have marked antioxidant effects. Hence, the present study was designed to evaluate the effect of A. cepa outer scale extract (ACE) against IR induced cognition and biochemical deficit in mice. ACE was prepared by maceration with 70% methanol and fractionated into ethylacetate and aqueous fractions. Bilateral common carotid artery occlusion for 10 min, followed by 24 h reperfusion, was used to induce cerebral IR injury. Following IR injury, ACE (100 and 200 mg/kg) was administered orally to animals for 7 days once daily. Behavioral outcomes (memory and sensorimotor functions) were evaluated using Morris water maze and neurological severity score. Cerebral infarct size, brain thiobarbituric acid reactive species, reduced glutathione, and superoxide dismutase activity were also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rose in brain oxidative stress in animals. The results of the present investigation revealed that ACE improved functional outcomes after cerebral IR injury which may be attributed to its antioxidant properties.

Keywords: allium cepa, cerebral ischemia, memory, sensorimotor

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794 Cytotoxic Activity of Marine-derived Fungi Trichoderma Longibrachiatum Against PANC-1 Cell Lines

Authors: Elin Julianti, Marlia Singgih, Masayoshi Arai, Jianyu Lin, Masteria Yunovilsa Putra, Muhammad Azhari, Agnia S. Muharam

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The search for a source of new medicinal compounds with anticancer activity from natural products has become important to resolve the ineffectiveness problem of pancreatic cancer therapy. Fungal marine microorganisms are prolific sources of bioactive natural products. In this present study, the ethyl acetate extract of cultured broth of Trichoderma longibrachiatum marine sponge-derived fungi exhibited selective cytotoxicity against human pancreatic carcinoma PANC-1 cells cultured under glucose-deficient conditions (IC50 = 98,4 µg/mL). The T. longibrachiatum was fermented by the static method at room temperature for 60 days. The culture broth was extracted using ethyl acetate by liquid-liquid extraction method. The liquid-liquid extraction was conducted toward the ethyl extract by using 90% MeOH-H₂O and n-|Hexane as a solvent. The extract of 90% MeOH-H₂O was fractionated by liquid extraction using by C₁₈ reversed-phase vacuum flash chromatography using mixtures of MeOH-H₂O, from 50:50 to 100:0, and 1% TFA MeOH as the eluents to yield six fractions. The fraction 2 (MeOH-H2O, 70:30) and fraction 3 (MeOH-H2O, 80:20) showed moderate cytotoxicity with IC50 value of 119.3 and 274.7 µg/mL, respectively. Fraction 4 (MeOH-H₂O, 90:10) showed the highest cytotoxicity activity with IC₅₀value of < 10 µg/mL. The chemical compounds of the fractions that are responsible for cytotoxic activity are potent for further investigation.

Keywords: cytotoxic activity, trichoderma longibrachiatum, marine-derived fungi, PANC-1 cell line

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793 Targeting NLRP3 Inflammasome Activation: A New Mechanism Underlying the Protective Effects of Nafamostat Against Acute Pancreatitis

Authors: Jiandong Ren, Lijun Zhao, Peng Chen

Abstract:

Nafamostat (NA), a synthetic broad-spectrum serine protease inhibitor, has been routinely employed for the treatment of acute pancreatitis (AP) and other inflammatory-associated diseases in some East Asia countries. Although the potent inhibitory activity against inflammation-related proteases such as thrombin, trypsin, kallikrein, plasmin, coagulation factors and complement factors is generally considered to be responsible for the anti-inflammatory effects of NA, precise target and molecular mechanism underlying the anti-inflammatory activity in the treatment of AP remain largely unknown yet. As an intracellular inflammatory signaling platform, the NOD-like receptor protein 3 (NLRP3) inflammasome is recently identified to be involved in the development of AP. In present study, we have revealed that NA alleviated pancreatic injury in a caerulein-induced AP model by inhibiting the NLRP3 inflammasome activation in pancreas. Mechanistically, NA interacted with HDAC6, a cytoplasmic deacetylase implicated in the NLRP3 inflammasome pathway, and efficiently abrogated the function of HDAC6. This property enabled NA to influence HDAC6 dependent NF-κB transcriptional activity and thus block NF-κB-driven transcriptional priming of NLRP3 inflammasome. Moreover, NA exerted the potential to interfere HDAC6-mediated intracellular transport of NLRP3, thereby leading to the failure of NLRP3 inflammasome activation. Our current work has provided valuable insight into the molecular mechanism underlying the immunomodulatory effect of NA in treatment of AP, highlighting its promising application in prevention of NLRP3 inflammasome-associated inflammatory pathological damage.

Keywords: acute pancreatitis, HDAC6, nafamostat, NLRP3 inflammasome

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792 Assessment of Sex Differences in Serum Urea and Creatinine Level in Response to Spinal Cord Injury Using Albino Rat Models

Authors: Waziri B. I., Elkhashab M. M.

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Background: One of the most serious consequences of spinal cord injury (SCI) is progressive deterioration of renal function mostly as a result of urine stasis and ascending infection of the paralyzed bladder. This necessitates for investigation of early changes in serum urea and creatinine and associated sex related differences in response to SCI. Methods: A total of 24 adult albino rats weighing above 150g were divided equally into two groups, a control and experimental group (n = 12) each containing an equal number of male and female rats. The experimental group animals were paralyzed by complete transection of spinal cord below T4 level after deep anesthesia with ketamine 75mg/kg. Blood samples were collected from both groups five days post SCI for analysis. Mean values of serum urea (mmol/L) and creatinine (µmol/L) for both groups were compared. P < 0.05 was considered as significant. Results: The results showed significantly higher levels (P < 0.05) of serum urea and creatinine in the male SCI models with mean values of 92.12 ± 0.98 and 2573 ± 70.97 respectively compared with their controls where the mean values for serum urea and creatinine were 6.31 ± 1.48 and 476. 95 ± 4.67 respectively. In the female SCI models, serum urea 13.11 ± 0.81 and creatinine 519.88 ± 31.13 were not significantly different from that of female controls with serum urea and creatinine levels of 11.71 ± 1.43 and 493.69 ± 17.10 respectively (P > 0.05). Conclusion: Spinal cord injury caused a significant increase in serum Urea and Creatinine levels in the male models compared to the females. This indicated that males might have higher risk of renal dysfunction following SCI.

Keywords: albino rats, creatinine, spinal cord injury (SCI), urea

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791 Educational Framework for Coaches on Injury Prevention in Adolescent Team Sports

Authors: Chantell Gouws, Lourens Millard, Anne Naude, Jan-Wessel Meyer, Brandon Stuwart Shaw, Ina Shaw

Abstract:

Background: Millions of South African youths participate in team sports, with netball and rugby being two of the largest worldwide. This increased participation and professionalism have resulted in an increase in the number of musculoskeletal injuries. Objective: This study examined the extent to which sport coaching knowledge translates to the injuries and prevention of injuries in adolescents participating in netball and rugby. Methods: Thirty-four South African sports coaches participated in the study. Eighteen netball coaches and 16 rugby coaches with varying levels of coaching experience were selected to participate. An adapted version of Nash and Sproule’s questionnaire was used to investigate the coaches’ knowledge with regards to sport-specific common injuries, injury prevention, fitness/conditioning, individual technique development, training programs, mental training, and preparation of players. The analysis of data was carried out using a number of different techniques outlined by Nash and Sproule (2012). These techniques were determined by the type of data. Descriptive data was used to provide statistical analysis. Quantitative data was used to determine the educational framework and knowledge of sports coaches on injury prevention. Numerical data was obtained through questions on sports injuries, as well as coaches’ sports knowledge levels. Participants’ knowledge was measured using a standardized scoring system. Results: For the 0-4 years of netball coaching experience, 76.4% of the coaches had knowledge and experience and 33.3% appropriate first aid knowledge, while for the 9-12 years and 13-16 years, 100% of the coaches had knowledge and experience and first aid knowledge. For the 0-4 years in rugby coaching experience, 59.1% had knowledge and experience and 71% the appropriate first aid knowledge; for the 17-20 years, 100% had knowledge and experience and first aid, while for higher or equal to 25 years, 45.5% had knowledge and experience. In netball, 90% of injuries consisted of ankle injuries, followed by 70% for knee, 50% for shoulder, 20% for lower leg, and 15% for finger injuries. In rugby, 81% of the injuries occurred at the knee, followed by 50% for the shoulder, 40% for the ankle, 31% for the head and neck, and 25% for hamstring injuries. Six hours of training resulted in a 13% chance of injuries in netball and a 32% chance in rugby. For 10 hours of training, the injury prevalence was 10% in netball and 17% in rugby, while 15 hours resulted in an injury incidence of 58% in netball players and a 25% chance in rugby players. Conclusion: This study highlights the need for coaches to improve their knowledge in relation to injuries and injury prevention, along with factors that act as a preventative measure and promotes players’ well-being.

Keywords: musculoskeletal injury, sport coaching, sport trauma

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790 Auto Rickshaw Impacts with Pedestrians: A Computational Analysis of Post-Collision Kinematics and Injury Mechanics

Authors: A. J. Al-Graitti, G. A. Khalid, P. Berthelson, A. Mason-Jones, R. Prabhu, M. D. Jones

Abstract:

Motor vehicle related pedestrian road traffic collisions are a major road safety challenge, since they are a leading cause of death and serious injury worldwide, contributing to a third of the global disease burden. The auto rickshaw, which is a common form of urban transport in many developing countries, plays a major transport role, both as a vehicle for hire and for private use. The most common auto rickshaws are quite unlike ‘typical’ four-wheel motor vehicle, being typically characterised by three wheels, a non-tilting sheet-metal body or open frame construction, a canvas roof and side curtains, a small drivers’ cabin, handlebar controls and a passenger space at the rear. Given the propensity, in developing countries, for auto rickshaws to be used in mixed cityscapes, where pedestrians and vehicles share the roadway, the potential for auto rickshaw impacts with pedestrians is relatively high. Whilst auto rickshaws are used in some Western countries, their limited number and spatial separation from pedestrian walkways, as a result of city planning, has not resulted in significant accident statistics. Thus, auto rickshaws have not been subject to the vehicle impact related pedestrian crash kinematic analyses and/or injury mechanics assessment, typically associated with motor vehicle development in Western Europe, North America and Japan. This study presents a parametric analysis of auto rickshaw related pedestrian impacts by computational simulation, using a Finite Element model of an auto rickshaw and an LS-DYNA 50th percentile male Hybrid III Anthropometric Test Device (dummy). Parametric variables include auto rickshaw impact velocity, auto rickshaw impact region (front, centre or offset) and relative pedestrian impact position (front, side and rear). The output data of each impact simulation was correlated against reported injury metrics, Head Injury Criterion (front, side and rear), Neck injury Criterion (front, side and rear), Abbreviated Injury Scale and reported risk level and adds greater understanding to the issue of auto rickshaw related pedestrian injury risk. The parametric analyses suggest that pedestrians are subject to a relatively high risk of injury during impacts with an auto rickshaw at velocities of 20 km/h or greater, which during some of the impact simulations may even risk fatalities. The present study provides valuable evidence for informing a series of recommendations and guidelines for making the auto rickshaw safer during collisions with pedestrians. Whilst it is acknowledged that the present research findings are based in the field of safety engineering and may over represent injury risk, compared to “Real World” accidents, many of the simulated interactions produced injury response values significantly greater than current threshold curves and thus, justify their inclusion in the study. To reduce the injury risk level and increase the safety of the auto rickshaw, there should be a reduction in the velocity of the auto rickshaw and, or, consideration of engineering solutions, such as retro fitting injury mitigation technologies to those auto rickshaw contact regions which are the subject of the greatest risk of producing pedestrian injury.

Keywords: auto rickshaw, finite element analysis, injury risk level, LS-DYNA, pedestrian impact

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789 Explanatory Variables for Crash Injury Risk Analysis

Authors: Guilhermina Torrao

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An extensive number of studies have been conducted to determine the factors which influence crash injury risk (CIR); however, uncertainties inherent to selected variables have been neglected. A review of existing literature is required to not only obtain an overview of the variables and measures but also ascertain the implications when comparing studies without a systematic view of variable taxonomy. Therefore, the aim of this literature review is to examine and report on peer-reviewed studies in the field of crash analysis and to understand the implications of broad variations in variable selection in CIR analysis. The objective of this study is to demonstrate the variance in variable selection and classification when modeling injury risk involving occupants of light vehicles by presenting an analytical review of the literature. Based on data collected from 64 journal publications reported over the past 21 years, the analytical review discusses the variables selected by each study across an organized list of predictors for CIR analysis and provides a better understanding of the contribution of accident and vehicle factors to injuries acquired by occupants of light vehicles. A cross-comparison analysis demonstrates that almost half the studies (48%) did not consider vehicle design specifications (e.g., vehicle weight), whereas, for those that did, the vehicle age/model year was the most selected explanatory variable used by 41% of the literature studies. For those studies that included speed risk factor in their analyses, the majority (64%) used the legal speed limit data as a ‘proxy’ of vehicle speed at the moment of a crash, imposing limitations for CIR analysis and modeling. Despite the proven efficiency of airbags in minimizing injury impact following a crash, only 22% of studies included airbag deployment data. A major contribution of this study is to highlight the uncertainty linked to explanatory variable selection and identify opportunities for improvements when performing future studies in the field of road injuries.

Keywords: crash, exploratory, injury, risk, variables, vehicle

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788 The Generation of Insulin Producing Cells from Human Mesenchymal Stem Cells by miR-375 and Anti-miR-9

Authors: Arefeh Jafarian, Mohammad Taghikani, Saied Abroun, Amir Allahverdi, Masoud Soleimani

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Introduction: The miRNAs have key roles in control of pancreatic islet development and insulin secretion. In this regards, current study investigated the pancreatic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) by up-regulation of miR-375 and down-regulation of miR-9 by lentiviruses containing miR-375 and anti-miR-9. Findings: After 21 days of induction, islet-like clusters containing insulin producing cells (IPCs) were confirmed by dithizone (DTZ) staining. The IPCs and β cell specific related genes and proteins were detected using qRT-PCR and immunofluorescence on days 7, 14 and 21 of differentiation. Glucose challenge test was performed at different concentrations of glucose as well as extracellular and intracellular insulin and C-peptide were assayed using ELISA kit. In derived IPCs by miR-375 alone are capable to express insulin and other endocrine specific transcription factors, the cells lack the machinery to respond to glucose. The differentiated hMSCs by miR-375 and anti-miR-9 lentiviruses could secrete insulin and c-peptide in a glucose-regulated manner. Conclusion: It was found that over-expression of miR-375 led to a reduction in levels of Mtpn protein in derived IPCs, while treatment with anti-miR-9 following miR-375 over-expression had synergistic effects on MSCs differentiation and insulin secretion in a glucose-regulated manner. The researchers reported that silencing of miR-9 increased OC-2 protein in IPCs that may contribute to the observed glucose-regulated insulin secretion. These findings highlight miRNAs functions in stem cells differentiation and suggest that they could be used as therapeutic tools for gene-based therapy in diabetes mellitus.

Keywords: diabetes, differentiation, MSCs, insulin producing cells, miR-375, miR-9

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787 Personalized Tissues and Organs Replacement – a Peek into the Future

Authors: Asaf Toker

Abstract:

Matricelf developed a technology that enables the production of autologous engineered tissue composed of matrix and cells derived from patients Omentum biopsy. The platform showed remarkable pre-clinical results for several medical conditions. The company recently licensed the technology that enabled scientist at Tel Aviv university that 3D printed a human heart from human cells and matrix for the first time in human history. The company plans to conduct its first human clinical trial for Acute Spinal Cord Injury (SCI) early in 2023.

Keywords: tissue engineering, regenerative medicine, spinal Cord Injury, autologous implants, iPSC

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786 Effects of Active Muscle Contraction in a Car Occupant in Whiplash Injury

Authors: Nisha Nandlal Sharma, Julaluk Carmai, Saiprasit Koetniyom, Bernd Markert

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Whiplash Injuries are usually associated with car accidents. The sudden forward or backward jerk to head causes neck strain, which is the result of damage to the muscle or tendons. Neck pain and headaches are the two most common symptoms of whiplash. Symptoms of whiplash are commonly reported in studies but the Injury mechanism is poorly understood. Neck muscles are the most important factor to study the neck Injury. This study focuses on the development of finite element (FE) model of human neck muscle to study the whiplash injury mechanism and effect of active muscle contraction on occupant kinematics. A detailed study of Injury mechanism will promote development and evaluation of new safety systems in cars, hence reducing the occurrence of severe injuries to the occupant. In present study, an active human finite element (FE) model with 3D neck muscle model is developed. Neck muscle was modeled with a combination of solid tetrahedral elements and 1D beam elements. Muscle active properties were represented by beam elements whereas, passive properties by solid tetrahedral elements. To generate muscular force according to inputted activation levels, Hill-type muscle model was applied to beam elements. To simulate non-linear passive properties of muscle, solid elements were modeled with rubber/foam material model. Material properties were assigned from published experimental tests. Some important muscles were then inserted into THUMS (Total Human Model for Safety) 50th percentile male pedestrian model. To reduce the simulation time required, THUMS lower body parts were not included. Posterior to muscle insertion, THUMS was given a boundary conditions similar to experimental tests. The model was exposed to 4g and 7g rear impacts as these load impacts are close to low speed impacts causing whiplash. The effect of muscle activation level on occupant kinematics during whiplash was analyzed.

Keywords: finite element model, muscle activation, neck muscle, whiplash injury prevention

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785 Allium Cepa Extract Provides Neuroprotection Against Ischemia Reperfusion Induced Cognitive Dysfunction and Brain Damage in Mice

Authors: Jaspal Rana, Alkem Laboratories, Baddi, Himachal Pradesh, India Chitkara University, Punjab, India

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Oxidative stress has been identified as an underlying cause of ischemia-reperfusion (IR) related cognitive dysfunction and brain damage. Therefore, antioxidant based therapies to treat IR injury are being investigated. Allium cepa L. (onion) is used as culinary medicine and is documented to have marked antioxidant effects. Hence, the present study was designed to evaluate the effect of A. cepa outer scale extract (ACE) against IR induced cognition and biochemical deficit in mice. ACE was prepared by maceration with 70% methanol and fractionated into ethylacetate and aqueous fractions. Bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion was used to induce cerebral IR injury. Following IR injury, ACE (100 and 200 mg/kg) was administered orally to animals for 7 days once daily. Behavioral outcomes (memory and sensorimotor functions) were evaluated using Morris water maze and neurological severity score. Cerebral infarct size, brain thiobarbituric acid reactive species, reduced glutathione, and superoxide dismutase activity was also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rise in brain oxidative stress in animals. The results of the present investigation revealed that ACE improved functional outcomes after cerebral IR injury, which may be attributed to its antioxidant properties.

Keywords: stroke, neuroprotection, ischemia reperfusion, herbal drugs

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784 Anethum graveolens Prevents Liver and Kidney Injury, Oxidative Stress and Inflammation in Mice Exposed to Nicotine Perinatally

Authors: Saleh N. Maodaa

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Perinatal exposure to nicotine imbalances the redox status in newborns. This study investigated the effect of Anethum graveolens (dill) extract on oxidative stress and tissue injury in the liver and kidney of mice newborns exposed to nicotine perinatally. Pregnant mice received nicotine (0.25 mg/kg) on gestational day 12 to day 5 after birth and/or A. graveolens extract on a gestational day 1 to day 15 after birth. Newborn mice exposed to nicotine showed multiple histopathological alterations in the kidney and liver, including inflammatory cell infiltration and degenerative changes. Nicotine exposure increased hepatic and renal reactive oxygen species (ROS), lipid peroxidation, tumor necrosis factor (TNF-_), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) (p < 0.001), and decreased antioxidant defenses (p < 0.001). A. graveolens supplementation significantly prevented liver and kidney injury, suppressed ROS generation (p < 0.001), lipid peroxidation (p < 0.001), and inflammatory response (p < 0.001), and enhanced antioxidant defenses. In addition, A. graveolens upregulated hepatic and renal Nrf2 and HO-1 mRNA and increased HO-1 activity in normal and nicotine-exposed mice. In conclusion, A. graveolens protects against perinatal nicotine-induced oxidative stress, inflammation, and tissue injury in the liver and kidney of newborn mice. A. graveolens upregulated hepatic and renal Nrf2/HO-1 signaling and enhanced antioxidant defenses in mice.

Keywords: dill, oxidative stress, cytokines, nicotine

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783 Rasagiline Improves Metabolic Function and Reduces Tissue Injury in the Substantia Nigra in Parkinson's Disease: A Longitudinal In-Vivo Advanced MRI Study

Authors: Omar Khan, Shana Krstevska, Edwin George, Veronica Gorden, Fen Bao, Christina Caon, NP-C, Carla Santiago, Imad Zak, Navid Seraji-Bozorgzad

Abstract:

Objective: To quantify cellular injury in the substantia nigra (SN) in patients with Parkinson's disease (PD) and to examine the effect of rasagiline of tissue injury in the SN in patients with PD. Background: N-acetylaspartate (NAA) quantified with MRS is a reliable marker of neuronal metabolic function. Fractional anisotropy (FA) and mean diffusivity (MD) obtained with DTI, characterize tissue alignment and integrity. Rasagline, has been shown to exert anti-apototic effect. We applied these advanced MRI techniques to examine: (i) the effect of rasagiline on cellular injury and metabolism in patients with early PD, and (ii) longitudinal changes seen over time in PD. Methods: We conducted a prospective longitudinal study in patients with mild PD, naive to dopaminergic treatment. The imaging protocol included multi-voxel proton-MRS and DTI of the SN, acquired on a 3T scanner. Scans were performed at baseline and month 3, during which the patient was on no treatment. At that point, rasagiline 1 mg orally daily was initiated and MRI scans are were obtained at 6 and 12 months after starting rasagiline. The primary objective was to compare changes during the 3-month period of “no treatment” to the changes observed “on treatment” with rasagiline at month 12. Age-matched healthy controls were also imaged. Image analysis was performed blinded to treatment allocation and period. Results: 25 patients were enrolled in this study. Compared to the period of “no treatment”, there was significant increase in the NAA “on treatment” period (-3.04 % vs +10.95 %, p= 0.0006). Compared to the period of “no treatment”, there was significant increase in following 12 month in the FA “on treatment” (-4.8% vs +15.3%, p<0.0001). The MD increased during “no treatment” and decreased in “on treatment” (+2.8% vs -7.5%, p=0.0056). Further analysis and clinical correlation are ongoing. Conclusions: Advanced MRI techniques quantifying cellular injury in the SN in PD is a feasible approach to investigate dopaminergic neuronal injury and could be developed as an outcome in exploratory studies. Rasagiline appears to have a stabilizing effect on dopaminergic cell loss and metabolism in the SN in PD, that warrants further investigation in long-term studies.

Keywords: substantia nigra, Parkinson's disease, MRI, neuronal loss, biomarker

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782 Shielding Engineered Islets with Mesenchymal Stem Cells Enhance Survival under Hypoxia by Inhibiting p38 MAPK

Authors: Bhawna Chandravanshi, Ramesh Bhonde

Abstract:

In the present study, we focused on the improvisation of islet survival in hypoxia. The Islet-like cell aggregates (ICAs) derived from Wharton's jelly mesenchymal stem cells (WJ-MSC) were cultured with and without WJ-MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin, Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitate the highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytokine analysis of the co-cultured ICAs revealed amplification of anti-inflammatory cytokine-like TGFβ and TNFα accompanied by depletion of pro-inflammatory cytokines. The increment in VEGF and PDGFa was also seen showing their ability to vascularize upon transplantation. This was further accompanied by reduction in total reactive oxygen species, nitric oxide, and super oxide ions and down-regulation of Caspase3, Caspase8, p53 and up regulation of Bcl2 confirming prevention of apoptosis in ICAs. There was a significant reduction in the expression of p38 protein in the presence of MSCs making the ICAs responsive to glucose. Taken together our data demonstrate for the first time that the WJ-MSC expressed pancreatic markers and their supplementation protected engineered islets against hypoxia, oxidative stress, and inflammatory cytokines by inhibiting p38 MAPK protein.

Keywords: hypoxia, islet-like cell aggregates, inflammatory cytokines, oxidative stress

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