Search results for: traumatic brain injury.

Authors: Scott Andersen

Abstract:

Perhaps simply and rather unadornedly, consciousness is having multiple goals for action and the continuously adjudication of such goals to implement action, referred to as the Maps of Meaning (MoM) Consciousness Theory. The MoM theory triangulates through three parallel corollaries, action (behavior), mechanism (morphology/pathophysiology), and goals (teleology). (1) An organism’s consciousness contains a fluid, nested goals. These goals are not intentionality, but intersectionality, embodiment meeting the world. i.e., Darwinian inclusive fitness or randomization, then survival of the fittest. These goals form via gradual descent under inclusive fitness, the goals being the abstraction of a ‘match’ between the evolutionary environment and organism. Human consciousness implements the brain efficiency hypothesis, genetics, epigenetics, and experience crystallize efficiencies, not necessitating best or objective but fitness, i.e., perceived efficiency based on one’s adaptive environment. These efficiencies are objectively arbitrary, but determine the operation and level of one’s consciousness, termed extreme thrownness. Since inclusive fitness drives efficiencies in physiologic mechanism, morphology and behavior (action) and originates one’s goals, embodiment is necessarily entangled to human consciousness as its the intersection of mechanism or action (both necessitating embodiment) occurring in the world that determines fitness. Perception is the operant process of consciousness and is the consciousness’ de facto goal adjudication process. Goal operationalization is fundamentally efficiency-based via one’s unique neuronal mapping as a byproduct of genetics, epigenetics, and experience. Perception involves information intake and information discrimination, equally underpinned by efficiencies of inclusive fitness via extreme thrownness. Perception isn’t a ‘frame rate,’ but Bayesian priors of efficiency based on one’s extreme thrownness. Consciousness and human consciousness is a modular (i.e., a scalar level of richness, which builds up like building blocks) and dimensionalized (i.e., cognitive abilities become possibilities as emergent phenomena at various modularities, like stratified factors in factor analysis). The meta dimensions of human consciousness seemingly include intelligence quotient, personality (five-factor model), richness of perception intake, and richness of perception discrimination, among other potentialities. Future consciousness research should utilize factor analysis to parse modularities and dimensions of human consciousness and animal models.

Keywords: consciousness, perception, prospection, embodiment

Procedia PDF Downloads 60

Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

Abstract:

One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

Procedia PDF Downloads 226

Authors: Viviane A. O. Silva, Angela M. Costa, Glaucia N. M. Hajj, Ana Preto, Aline Tansini, Martin Roffé, Peter Jordan, Rui M. Reis

Abstract:

Autophagy is a recycling and degradative system suggested to be a major cell death pathway in cancer cells. Autophagy pathway is interconnected with the endocytosis pathways sharing the same ultimate lysosomal destination. Lysosomes are crucial regulators of cell homeostasis, responsible to downregulate receptor signalling and turnover. It seems highly likely that derailed endocytosis can make major contributions to several hallmarks of cancer. WNK2, a member of the WNK (with-no-lysine [K]) subfamily of protein kinases, had been found downregulated by its promoter hypermethylation, and has been proposed to act as a specific tumour-suppressor gene in brain tumors. Although some contradictory studies indicated WNK2 as an autophagy modulator, its role in cancer cell death is largely unknown. There is also growing evidence for additional roles of WNK kinases in vesicular traffic. Aim: To evaluate the role of WNK2 in autophagy and endocytosis on glioma context. Methods: Wild-type (wt) A172 cells (WNK2 promoter-methylated), and A172 transfected either with an empty vector (Ev) or with a WNK2 expression vector, were used to assess the cellular basal capacities to promote autophagy, through western blot and flow-cytometry analysis. Additionally, we evaluated the effect of WNK2 on general endocytosis trafficking routes by immunofluorescence. Results: The re-expression of ectopic WNK2 did not interfere with autophagy-related protein light chain 3 (LC3-II) expression levels as well as did not promote mTOR signaling pathway alteration when compared with Ev or wt A172 cells. However, the restoration of WNK2 resulted in a marked increase (8 to 92,4%) of Acidic Vesicular Organelles formation (AVOs). Moreover, our results also suggest that WNK2 cells promotes delay in uptake and internalization rate of cholera toxin B and transferrin ligands. Conclusions: The restoration of WNK2 interferes in vesicular traffic during endocytosis pathway and increase AVOs formation. This results also suggest the role of WNK2 in growth factor receptor turnover related to cell growth and homeostasis and associates one more time, WNK2 silencing contribution in genesis of gliomas.

Keywords: autophagy, endocytosis, glioma, WNK2

Procedia PDF Downloads 370

Authors: Tracey Lion-Cachet

Abstract:

Eating disorders typically manifest in adolescence and are notoriously difficult to treat. There are two notable reasons for this. Firstly, research consistently demonstrates that early intervention is a critical mediator of prognosis, with early intervention leading to a better prognosis. However, because eating disorders do not originate as full-syndrome diagnoses but rather as prodromal cases, they often go undetected; by the time symptoms meet diagnostic criteria, they have become recalcitrant. Another interrelated issue is motivation to change. Research demonstrates that in the early stages of an eating disorder, adolescents are highly resistant to change, and motivation increases only once symptoms have shifted from egosyntonic to egodystonic in nature. The purpose of this project was to design a prevention model based on the social psychology paradigm of Entertainment-Education, which embeds messages within the genre of film as a means of affecting change. The resulting project was a narrative screenplay targeting teenagers/young adults from diverse backgrounds. The goals of the project were to create a film script that, if ultimately made into a film, could serve to: 1) interrupt symptom progression and improve prognosis through early intervention; 2) incorporate techniques from third-wave cognitive behavioral treatment models, acceptance and commitment therapy (ACT) and rational recovery (RR), with a focus on the effects of mindfulness as a means of informing recovery; 3) target issues to do with motivation to change by shifting the perception of eating disorders from culturally specific psychiatric illnesses to habit-based brain wiring issues. Nine licensed clinicians were asked to evaluate two excerpts taken from the final script. They subsequently provided feedback on a Likert-scale, which assessed whether the script had achieved its goals. Overall, evaluators agreed that the project’s etiological and intervention models have the potential to inspire change and serve as an effective means of prevention and treatment of eating disorders. However, one-third of the evaluators did not find the content developmentally appropriate. This is a notable limitation to the study and will need to be addressed in the larger script before the final project can potentially be targeted to a teenage and young adult audience.

Keywords: adolescents, eating disorders, pediatrics, entertainment-education, mindfulness-based intervention, prevention

Procedia PDF Downloads 91

Authors: Taikchan Lildar, Ayesha Samad, Suraj Sookhu

Abstract:

Atrial fibrillation with rapid ventricular response results in the loss of atrial kick and shortened ventricular filling time, which often leads to decompensated heart failure. Pharmacologic rhythm control is the treatment of choice, and patients frequently benefit from the restoration of sinus rhythm. When pharmacologic treatment is unsuccessful or a patient declines hemodynamically, direct cardioversion is the treatment of choice. Torsades de pointes or “twisting of the points'' in French, is a rare but under-appreciated risk of cardioversion therapy and accounts for a significant number of sudden cardiac death each year. A 61-year-old female with no significant past medical history presented to the Emergency Department with worsening dyspnea. An electrocardiogram showed atrial fibrillation with rapid ventricular response, and a chest X-ray was significant for bilateral pulmonary vascular congestion. Full-dose anticoagulation and diuresis were initiated with moderate improvement in symptoms. A transthoracic echocardiogram revealed biventricular systolic dysfunction with a left ventricular ejection fraction of 30%. After consultation with an electrophysiologist, the consensus was to proceed with the restoration of sinus rhythm, which would likely improve the patient’s heart failure symptoms and possibly the ejection fraction. A transesophageal echocardiogram was negative for left atrial appendage thrombus; the patient was treated with a loading dose of amiodarone and underwent successful direct current cardioversion with 200 Joules. The patient was placed on telemetry monitoring for 24 hours and was noted to have frequent premature ventricular contractions with subsequent degeneration to torsades de pointes. The patient was found unresponsive and pulseless; cardiopulmonary resuscitation was initiated with cardioversion, and return of spontaneous circulation was achieved after four minutes to normal sinus rhythm. Post-cardiac arrest electrocardiogram showed sinus bradycardia with heart-rate corrected QT interval of 592 milliseconds. The patient continued to have frequent premature ventricular contractions and required two additional cardioversions to achieve a return of spontaneous circulation with intravenous magnesium and lidocaine. An automatic implantable cardioverter-defibrillator was subsequently implanted for secondary prevention of sudden cardiac death. The backup pacing rate of the automatic implantable cardioverter-defibrillator was set higher than usual in an attempt to prevent premature ventricular contractions-induced torsades de pointes. The patient did not have any further ventricular arrhythmias after implantation of the automatic implantable cardioverter-defibrillator. Overdrive pacing is a method utilized to treat premature ventricular contractions-induced torsades de pointes by preventing a patient’s susceptibility to R on T-wave-induced ventricular arrhythmias. Pacing at a rate of 90 beats per minute succeeded in controlling the arrhythmia without the need for traumatic cardiac defibrillation. In our patient, conversion of atrial fibrillation with rapid ventricular response to normal sinus rhythm resulted in a slower heart rate and an increased probability of premature ventricular contraction occurring on the T-wave and ensuing ventricular arrhythmia. This case highlights direct current cardioversion for atrial fibrillation with rapid ventricular response resulting in persistent ventricular arrhythmia requiring an automatic implantable cardioverter-defibrillator placement with overdrive pacing to prevent a recurrence.

Keywords: refractory atrial fibrillation, atrial fibrillation, overdrive pacing, torsades de pointes

Procedia PDF Downloads 147

Authors: Weeradej Cheewapattananuwong, Keeree Srivichian, Godchamon Somchai, Wasin Phusanong, Nontawat Yoddamnern

Abstract:

Natural rubber used for traffic devices in Thailand has been developed and researched for several years. When compared with Dry Rubber Content (DRC), the quality of Rib Smoked Sheet (RSS) is better. However, the cost of admixtures, especially CaCO₃ and sulphur, is higher than the cost of RSS itself. In this research, Flexible Guideposts and Rubber Fender Barriers (RFB) are taken into consideration. In case of flexible guideposts, the materials used are both RSS and DRC60%, but for RFB, only RSS is used due to the controlled performance tests. The objective of flexible guideposts and RFB is to decrease a number of accidents, fatal rates, and serious injuries. Functions of both devices are to save road users and vehicles as well as to absorb impact forces from vehicles so as to decrease of serious road accidents. This leads to the mitigation methods to remedy the injury of motorists, form severity to moderate one. The solution is to find the best practice of traffic devices using natural rubber under the engineering concepts. In addition, the performances of materials, such as tensile strength and durability, are calculated for the modulus of elasticity and properties. In the laboratory, the simulation of crashes, finite element of materials, LRFD, and concrete technology methods are taken into account. After calculation, the trials' compositions of materials are mixed and tested in the laboratory. The tensile test, compressive test, and weathering or durability test are followed and based on ASTM. Furthermore, the Cycle-Repetition Test of Flexible Guideposts will be taken into consideration. The final decision is to fabricate all materials and have a real test section in the field. In RFB test, there will be 13 crash tests, 7 Pickup Truck tests, and 6 Motorcycle Tests. The test of vehicular crashes happens for the first time in Thailand, applying the trial and error methods; for example, the road crash test under the standard of NCHRP-TL3 (100 kph) is changed to the MASH 2016. This is owing to the fact that MASH 2016 is better than NCHRP in terms of speed, types, and weight of vehicles and the angle of crash. In the processes of MASH, Test Level 6 (TL-6), which is composed of 2,270 kg Pickup Truck, 100 kph, and 25 degree of crash-angle is selected. The final test for real crash will be done, and the whole system will be evaluated again in Korea. The researchers hope that the number of road accidents will decrease, and Thailand will be no more in the top tenth ranking of road accidents in the world.

Keywords: LRFD, load and resistance factor design, ASTM, american society for testing and materials, NCHRP, national cooperation highway research program, MASH, manual for assessing safety hardware

Procedia PDF Downloads 128

Authors: Mohammad Afzal Khan, Fatimah Alanazi, Hala Abdalrahman Ahmed, Talal Shamma, Kilian Kelly, Mohammed A. Hammad, Abdullah O. Alawad, Abdullah Mohammed Assiri, Dieter Clemens Broering

Abstract:

Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite the remarkable short-term recovery, long-term lung survival continues to face several significant challenges, including chronic rejection and severe toxic side-effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The Cymerus™ manufacturing facilitates the production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection. Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune-tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c→C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/ at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium and collagen deposition during rejection. We demonstrated that iPSC-derived MSC treatment leads to significant increase in tissue expression of hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post-transplantation. Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune-tolerance and rescue allograft from sustained hypoxic/ischemic phase and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.

Keywords: stem cell therapy, immunotolerance, regulatory T cells, hypoxia and ischemia, microvasculature

Procedia PDF Downloads 158

Authors: K. C. M. Wong, C. P. Y. Cheng, K. Y. Chan, G. S. C. Fung, T. F. O. Lau, K. F. C. Leung, J. P. C. Fok

Abstract:

Hospital Authority (HA) is the statutory body to manage all public hospitals in Hong Kong. Occupational Care Medicine Service (OMCS) is an in-house multi-disciplinary team responsible for injury management in HA. Hospital administrative services (AS) provides essential support in hospital daily operation to facilitate the provision of quality healthcare services. An occupational health enhancement program in Tai Po Hospital (TPH) domestic service supporting unit (DSSU) was piloted in 2013 with satisfactory outcome, the keys to success were staff engagement and management support. Riding on the success, the program was rolled out to another 5 AS departments of Alice Ho Miu Ling Nethersole Hospital (AHNH) and TPH in 2015. This paper highlights the indispensable components of disability management and occupational health enhancement program in hospital settings. Objectives: 1) Facilitate workplace to support staff with health affecting work problem, 2) Enhance staff’s occupational health. Methodology: Hospital Occupational Safety and Health (OSH) team and AS departments (catering, linen services, and DSSU) of AHNH and TPH worked closely with OMCS. Focus group meetings and worksite visits were conducted with frontline staff engagement. OSH hazards were identified with corresponding OSH improvement measures introduced, e.g., invention of high dusting device to minimize working at height; tailor-made linen cart to minimize back bending at work, etc. Specific MHO trainings were offered to each AS department. A disability management workshop was provided to supervisors in order to enhance their knowledge and skills in return-to-work (RTW) facilitation. Based on injured staff's health condition, OMCS would provide work recommendation, and RTW plan was formulated with engagement of staff and their supervisors. Genuine communication among stakeholders with expectation management paved the way for realistic goals setting and success in our program. Outcome: After implementation of the program, a significant drop of 26% in musculoskeletal disorders related sickness absence day was noted in 2016 as compared to the average of 2013-2015. The improvement was postulated by innovative OSH improvement measures, teamwork, staff engagement and management support. Staff and supervisors’ feedback were very encouraging that 90% respondents rated very satisfactory in program evaluation. This program exemplified good work sharing among departments to support staff in need.

Keywords: disability management, occupational health, return to work, occupational medicine

Procedia PDF Downloads 212

Authors: Karan Sharma, Ajay Kumar

Abstract:

Epileptic seizure is a type of disease due to which electrical charge in the brain flows abruptly resulting in abnormal activity by the subject. One percent of total world population gets epileptic seizure attacks.Due to abrupt flow of charge, EEG (Electroencephalogram) waveforms change. On the display appear a lot of spikes and sharp waves in the EEG signals. Detection of epileptic seizure by using conventional methods is time-consuming. Many methods have been evolved that detect it automatically. The initial part of this paper provides the review of techniques used to detect epileptic seizure automatically. The automatic detection is based on the feature extraction and classification patterns. For better accuracy decomposition of the signal is required before feature extraction. A number of parameters are calculated by the researchers using different techniques e.g. approximate entropy, sample entropy, Fuzzy approximate entropy, intrinsic mode function, cross-correlation etc. to discriminate between a normal signal & an epileptic seizure signal.The main objective of this review paper is to present the variations in the EEG signals at both stages (i) Interictal (recording between the epileptic seizure attacks). (ii) Ictal (recording during the epileptic seizure), using most appropriate methods of analysis to provide better healthcare diagnosis. This research paper then investigates the effects of a noninvasive healing therapy on the subjects by studying the EEG signals using latest signal processing techniques. The study has been conducted with Reiki as a healing technique, beneficial for restoring balance in cases of body mind alterations associated with an epileptic seizure. Reiki is practiced around the world and is recommended for different health services as a treatment approach. Reiki is an energy medicine, specifically a biofield therapy developed in Japan in the early 20th century. It is a system involving the laying on of hands, to stimulate the body’s natural energetic system. Earlier studies have shown an apparent connection between Reiki and the autonomous nervous system. The Reiki sessions are applied by an experienced therapist. EEG signals are measured at baseline, during session and post intervention to bring about effective epileptic seizure control or its elimination altogether.

Keywords: EEG signal, Reiki, time consuming, epileptic seizure

Procedia PDF Downloads 406

Authors: Soniya Nityanand, Ekta Minocha, Manali Jain, Rohit Anthony Sinha, Chandra Prakash Chaturvedi

Abstract:

Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: amniotic fluid stem cells, acute renal failure, autophagy, cisplatin

Procedia PDF Downloads 104

Authors: Qiaoyue Kuang, Yang Li, Mizuki Endo, Takeaki Ozawa

Abstract:

G protein-coupled receptors (GPCR) are the largest family of receptor proteins that detect molecules outside the cell and activate cellular responses. Of the GPCRs, dopamine receptors, which recognize extracellular dopamine, are essential to mammals due to their roles in numerous physiological events, including autonomic movement, hormonal regulation, emotions, and the reward system in the brain. To precisely understand the physiological roles of dopamine receptors, it is important to spatiotemporally control the signaling mediated by dopamine receptors, which is strongly dependent on their surface expression. Conventionally, chemical-induced interactions were applied to trigger the endocytosis of cell surface receptors. However, these methods were subjected to diffusion and therefore lacked temporal and special precision. To further understand the receptor-mediated signaling and to control the plasma membrane expression of receptors, an optogenetic tool called E-fragment was developed. The C-terminus of a light-sensitive photosensory protein cyptochrome2 (CRY2) was attached to β-Arrestin, and the E-fragment was generated by fusing the C-terminal peptide of vasopressin receptor (V2R) to CRY2’s binding partner protein CIB. The CRY2-CIB heterodimerization triggered by blue light stimulation brings β-Arrestin to the vicinity of membrane receptors and results in receptor endocytosis. In this study, the E-fragment system was applied to dopamine receptors 1 and 2 (DRD1 and DRD2) to control dopamine signaling. First, confocal fluorescence microscope observation qualitatively confirmed the light-induced endocytosis of E-fragment fused receptors. Second, NanoBiT bioluminescence assay verified quantitatively that the surface amount of E-fragment labeled receptors decreased after light treatment. Finally, GloSensor bioluminescence assay results suggested that the E-fragment-dependent receptor light-induced endocytosis decreased cAMP production in DRD1 signaling and attenuated the inhibition effect of DRD2 on cAMP production. The developed optogenetic tool was able to induce receptor endocytosis by external light, providing opportunities to further understand numerous physiological activities by controlling receptor-mediated signaling spatiotemporally.

Keywords: dopamine receptors, endocytosis, G protein-coupled receptors, optogenetics

Procedia PDF Downloads 102

Authors: Fatimah Abd Elghani, Raymonde Szargel, Vered Shani, Hazem Safory, Haya Hamza, Mor Savyon, Ruth Rott, Rina Bandopadhyay, Simone Engelender

Abstract:

Background: PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. Down regulation of PINK1 results in abnormal mitochondrial morphology and altered membrane potential. Although PINK1 has a predicted mitochondrial import sequence, it’s cellular, and submitochondrial localization remains unclear, in part because it is rapidly degraded. In this work, we investigated the mechanisms involved in PINK1 degradation and how this may affect PINK1 stability and function, with implications for mitochondrial function in PD. In addition, pharmacological inhibition of proteasome activity was shown to lead to PINK1 accumulation, indicating that PINK1 degradation depends on the ubiquitin-proteasome system (UPS). Methods: Using co-immunoprecipitation assays, we identified E3 ubiquitin ligase SIAH1 as a PINK1-interacting protein in HEK293 cells as well as on rat brain tissues. In addition, we determined the effect of SIAH 1, SIAH2 and Parkin on PINK1 steady-state levels by Western blot analysis, and checked their possibility to ubiquitinate and mediate PINK1 degradation through the proteasome carried out in vivo ubiquitination experiments. Results: We have obtained results showing that SIAH-1 interacts with and ubiquitinates PINK1. The ubiquitination promoted by SIAH-1 leads to the proteasomal degradation of PINK1. We confirmed these findings by knocking down SIAH-1 and observing important accumulation of PINK1 in cells. Besides, we found that SIAH-1 decreases PINK1 steady-state levels but not the E3 ligase Parkin. We also investigated the interaction of SIAH-1 with PINK1 disease mutants and its ability to promote their ubiquitination and degradation. Although, no clear difference in the ability of SIAH-1 to promote the degradation of PINK1 disease mutants was observed. It is possible that dysfunction of proteasomal activity in the disease may lead to the accumulation and aggregation of ubiquitinated PINK1 in patients with PINK1 mutations, with possible implications to the pathogenesis of PD. Conclusions: Here, we demonstrated that SIAH-1 ubiquitinates and promotes the degradation of PINK1. In addition, SIAH-1 represents now a target that may help the improvement of mitophagy in PD. Further investigations needed to understand how mitophagy is regulated by PINK1-SIAH-1 axis to provide targets for future therapeutics.

Keywords: PD, Parkinson's disease, PINK1, PTEN-induced kinase1, SIAH, seven in absentia homolog, SN, substantia nigra

Procedia PDF Downloads 142

Authors: Jennifer A. Kowalkowski

Abstract:

Production agriculture (farming) is a physically, emotionally, and cognitively stressful occupation, where workers have little control over the stressors that impact both their work and their lives. In an occupation already rife with hazards, these occupational-related stressors have been shown to increase farm workers’ risks for illness, injury, disability, and death associated with their work. Despite efforts to mitigate the negative health effects from occupational-related stress (ORS) and to promote health and well-being (HWB) among farmers in the US, marked improvements have not been attained. Social support accessed through social networks has been shown to buffer against the negative health effects from stress, yet no studies have directly examined these relationships among farmers. The purpose of this study was to use social network analysis to explore the social networks of farm owner-operators and the social supports available to them for mitigating the negative health effects of ORS. A convenience sample of 71 farm owner-operators from a Midwestern County in the US completed and returned a mailed survey (55.5% response rate) that solicited information about their social networks related to ORS. Farmers reported an average of 2.4 individuals in their personal networks and higher levels of comfort discussing ORS with female network members. Farmers also identified few connections (3.4% density) and indicated low comfort with members of affiliation networks specific to ORS. Findings from this study highlighted that farmers accessed different social networks and resources for their personal HWB than for issues related to occupational(farm-related) health and safety. In addition, farmers’ social networks for personal HWB were smaller, with different relational characteristics than reported in studies of farmers’ social networks related to occupational health and safety. Collectively, these findings suggest that farmers conceptualize personal HWB differently than farm health and safety. Therefore, the same research approaches and targets that guide occupational health and safety research may not be appropriate for personal HWB for farmers. Interventions and programming targeting ORS and HWB have largely been offered through the same platforms or mechanisms as occupational health and safety programs. This may be attributed to the significant overlap between the farm as a family business and place of residence, or that ORS stems from farm-related issues. However, these assumptions translated to health research of farmers and farm families from the occupational health and safety literature have not been directly studied or challenged. Thismay explain why past interventions have not been effective at improving health outcomes for farmers and farm families. A close examination of findings from this study raises important questions for researchers who study agricultural health. Findings from this study have significant implications for future research agendas focused on addressing ORS, HWB, and health disparities for farmersand farm families.

Keywords: agricultural health, occupational-related stress, social networks, well-being

Procedia PDF Downloads 108

Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

Abstract:

With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

Procedia PDF Downloads 138

Authors: Bao Li, Aike Qiao, Gaoyang Li, Youjun Liu

Abstract:

Background: Lumped parameter model (LPM) is a common numerical model for hemodynamic calculation. LPM uses circuit elements to simulate the human blood circulatory system. Physiological indicators and characteristics can be acquired through the model. However, due to the different physiological indicators of each individual, parameters in LPM should be personalized in order for convincing calculated results, which can reflect the individual physiological information. This study aimed to develop an automatic and effective optimization method to personalize the parameters in LPM of the blood circulatory system, which is of great significance to the numerical simulation of individual hemodynamics. Methods: A closed-loop LPM of the human blood circulatory system that is applicable for most persons were established based on the anatomical structures and physiological parameters. The patient-specific physiological data of 5 volunteers were non-invasively collected as personalized objectives of individual LPM. In this study, the blood pressure and flow rate of heart, brain, and limbs were the main concerns. The collected systolic blood pressure, diastolic blood pressure, cardiac output, and heart rate were set as objective data, and the waveforms of carotid artery flow and ankle pressure were set as objective waveforms. Aiming at the collected data and waveforms, sensitivity analysis of each parameter in LPM was conducted to determine the sensitive parameters that have an obvious influence on the objectives. Simulated annealing was adopted to iteratively optimize the sensitive parameters, and the objective function during optimization was the root mean square error between the collected waveforms and data and simulated waveforms and data. Each parameter in LPM was optimized 500 times. Results: In this study, the sensitive parameters in LPM were optimized according to the collected data of 5 individuals. Results show a slight error between collected and simulated data. The average relative root mean square error of all optimization objectives of 5 samples were 2.21%, 3.59%, 4.75%, 4.24%, and 3.56%, respectively. Conclusions: Slight error demonstrated good effects of optimization. The individual modeling algorithm developed in this study can effectively achieve the individualization of LPM for the blood circulatory system. LPM with individual parameters can output the individual physiological indicators after optimization, which are applicable for the numerical simulation of patient-specific hemodynamics.

Keywords: blood circulatory system, individual physiological indicators, lumped parameter model, optimization algorithm

Procedia PDF Downloads 137

Authors: Dr. Jenit Gandhi, Dr. Manojith SS, Dr. Nakul GV, Dr. Sharath Honnani, Dr. Shaurav Ghosh, Dr. Neel Shetty, Dr. Nagabhushan JS, Dr. Manish Joshi

Abstract:

Introduction: Acute pancreatitis is an inflammatory condition of the pancreas which begins in pancreatic acinar cells and triggers local inflammation that may progress to systemic inflammatory response (SIRS) and causing distant organ involvement and its function and ending up with multiple organ dysfunction syndromes (MODS). Aim: A comparative study in acute pancreatitis to find out the effectiveness of early addition of Ulinastatin to current standard care in Indian subjects . Methodology: A current prospective observational study is done during study period of 1year (Dec 2018 –Dec 2019) duration to evaluate the effect of early addition of Ulinastatin to the current standard treatment and its efficacy to reduce the early complication, analgesic requirement and duration of hospital stay in patients with Acute Pancreatitis. Results: In the control group 25 were males and 05 were females. In the test group 18 were males and 12 females. Majority was in the age group between 30 - 70 yrs of age with >50% in the 30-50yrs age group in both test and control groups. The VAS was median grade 3 in control group as compared to median grade 2 in test group , the pain was more in the initial 2 days in test group compared to 4 days in test group , the analgesic requirement was used for more in control group (median 6) to test group( median 3 days ). On follow up after 5 days for a period of 2 weeks none of the patients in the test group developed any complication. Where as in the control group 8 patients developed pleural effusion, 04-Pseudopancreatic cyst, 02 – patient developed portal vein and splenic vein thrombosis, 02 patients – ventilator with ARDS which were treated symptomatically whereas in test group 02 patient developed pleural effusions and 01 pseudo pancreatic cyst with splenic artery aneurysm, 01 – patient with AKI and MODS symptomatically treated. The duration of hospital stay for a median period of 4 days (2 – 7 days) in test group and 7 days (4 -10 days) in control group. All patients were able to return to normal work on an average of 5days compared 8days in control group, the difference was significant. Conclusion:The study concluded that early addition of Ulinastatin to current standard treatment of acute Pancreatitis is effective in reducing pain, early complication and duration of hospital stay in Indian subject

Keywords: Ulinastatin, VAS – visual analogue score , AKI – acute kidney injury , ARDS – acute respiratory distress syndrome

Procedia PDF Downloads 122

Authors: Ming-Dong Wang, Abigail F. Ruby, Michelle E. Ross

Abstract:

Methylphenidate is a first-line treatment drug for attention deficit hyperactivity disorder (ADHD), a common mental health disorder in children and adolescents. Over the last several decades, the rate of children and adolescents using ADHD medication has been increasing in many countries. A recent study found that the prevalence of ADHD medication use among children aged 3-18 years increased in 13 different world regions between 2001 and 2015, where the absolute increase ranged from 0.02 to 0.26% per year. The goal of this study was to examine the use of methylphenidate in Canadian children and its associated adverse reactions. Methylphenidate use information among young Canadians aged 0-14 years was extracted from IQVIA data on prescriptions dispensed by pharmacies between April 2014 and June 2020. The adverse reaction information associated with methylphenidate use was extracted from the Canada Vigilance database for the same time period. Methylphenidate use trends were analyzed based on sex, age group (0-4 years, 5-9 years, and 10-14 years), and geographical location (province). The common classes of adverse reactions associated with methylphenidate use were sorted, and the relative risks associated with methylphenidate use as compared with two second-line amphetamine medications for ADHD were estimated. This study revealed that among Canadians aged 0-14 years, every 100 people used about 25 prescriptions (or 23,000 mg) of methylphenidate per year during the study period, and the use increased with time. Boys used almost three times more methylphenidate than girls. The amount of drug used was inversely associated with age: Canadians aged 10-14 years used nearly three times as many drugs compared to those aged 5-9 years. Seasonal methylphenidate use patterns were apparent among young Canadians, but the seasonal trends differed among the three age groups. Methylphenidate use varied from region to region, and the highest methylphenidate use was observed in Quebec, where the use of methylphenidate was at least double that of any other province. During the study period, Health Canada received 304 adverse reaction reports associated with the use of methylphenidate for Canadians aged 0-14 years. The number of adverse reaction reports received for boys was 3.5 times higher than that for girls. The three most common adverse reaction classes were psychiatric disorders, nervous system disorders and injury, poisoning procedural complications. The number one commonly reported adverse reaction for boys was aggression (11.2%), while for girls, it was a tremor (9.6%). The safety profile in terms of adverse reaction classes associated with methylphenidate use was similar to that of the selected control products. Methylphenidate is a commonly used pharmaceutical product in young Canadians, particularly in the province of Quebec. Boys used approximately three times more of this product as compared to girls. Future investigation is needed to determine what factors are associated with the observed geographic variations in Canada.

Keywords: adverse reaction risk, methylphenidate, prescription trend, use variation

Procedia PDF Downloads 160

Authors: Eoin Kirwan, Christopher Nulty, Declan Browne

Abstract:

The professional ice hockey season consists of approximately 60 regular season games with periods of fixture congestion occurring several times in the average season. These periods of congestion provide limited time for recovery, exposing the athletes to the risk of competing whilst not fully recovered. Although a body of research is growing with respect to monitoring fatigue, particularly during periods of congested fixtures in team sports such as rugby and soccer, it has received little to no attention thus far in ice hockey athletes. Consequently, there is limited knowledge on monitoring tools that might effectively detect a fatigue response and the magnitude of fatigue that can accumulate when recovery is limited by competitive fixtures. The benefit of quantifying and establishing fatigue status is the ability to optimise training and provide pertinent information on player health, injury risk, availability and readiness. Some commonly used methods to assess fatigue and recovery status of athletes include the use of perceived fatigue and wellbeing questionnaires, tests of muscular force and ratings of perceive exertion (RPE). These measures are widely used in popular team sports such as soccer and rugby and show promise as assessments of fatigue and recovery status for ice hockey athletes. As part of a larger study, this study explored the magnitude of changes in adductor muscle strength after game play and throughout a period of fixture congestion and examined the relationship between internal game load and perceived wellbeing with adductor muscle strength. Methods 8 professional ice hockey players from a British Elite League club volunteered to participate (age = 29.3 ± 2.49 years, height = 186.15 ± 6.75 cm, body mass = 90.85 ± 8.64 kg). Prior to and after competitive games each player performed trials of the adductor squeeze test at 0˚ hip flexion with the lead investigator using hand-held dynamometry. Rate of perceived exertion was recorded for each game and from data of total ice time individual session RPE was calculated. After each game players completed a 5- point questionnaire to assess perceived wellbeing. Data was collected from six competitive games, 1 practice and 36 hours post the final game, over a 10 – day period. Results Pending final data collection in February Conclusions Pending final data collection in February.

Keywords: Conjested fixtures, fatigue monitoring, ice hockey, readiness

Procedia PDF Downloads 142

Authors: Xi Chen, King-Yip Cheng

Abstract:

Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

Procedia PDF Downloads 67

Authors: Cathal Merz, Gareth O’Donnell

Abstract:

Coil reinforced thin-walled (CRTW) tubes are used in medicine to treat problems affecting blood vessels within the body through minimally invasive procedures. The CRTW tube considered in this research makes up part of such a device and is inserted into the patient via their femoral or brachial arteries and manually navigated to the site in need of treatment. This procedure replaces the requirement to perform open surgery but is limited by reduction of blood vessel lumen diameter and increase in tortuosity of blood vessels deep in the brain. In order to maximize the capability of these procedures, CRTW tube devices are being manufactured with decreasing wall thicknesses in order to deliver treatment deeper into the body and to allow passage of other devices through its inner diameter. This introduces significant stresses to the device materials which have resulted in an observed increase in the breaking of the proximal segment of the device into two separate pieces after it has failed by buckling. As there is currently no international standard for measuring the mechanical properties of these CRTW tube devices, it is difficult to accurately analyze this problem. The aim of the current work is to address this discrepancy in the biomedical device industry by developing a measurement system that can be used to quantify the effect of process and design changes on CRTW tube performance, aiding in the development of better performing, next generation devices. Using materials testing frames, micro-computed tomography (micro-CT) imaging, experiment planning, analysis of variance (ANOVA), T-tests and regression analysis, test methods have been developed for assessing the impact of process and design changes on the device. The major findings of this study have been an insight into the suitability of buckle and three-point bend tests for the measurement of the effect of varying processing factors on the device’s performance, and guidelines for interpreting the output data from the test methods. The findings of this study are of significant interest with respect to verifying and validating key process and design changes associated with the device structure and material condition. Test method integrity evaluation is explored throughout.

Keywords: neurovascular catheter, coil reinforced tube, buckling, three-point bend, tensile

Procedia PDF Downloads 117

Authors: Rema Vazhappilly, Tapas Das

Abstract:

Oleic acid is a cis unsaturated fatty acid and is known to be a partially essential fatty acid due to its limited endogenous synthesis during pregnancy and lactation. Previous studies have demonstrated the role of oleic acid in neuronal differentiation and brain phospholipid synthesis. These evidences indicate a major role for oleic acid in learning and memory. Interestingly, oleic acid has been shown to enhance hippocampal long term potentiation (LTP), the physiological correlate of long term synaptic plasticity. However the effect of oleic acid on short term synaptic plasticity has not been investigated. Short term potentiation (STP) is the physiological correlate of short term synaptic plasticity which is the key underlying molecular mechanism of short term memory and neuronal information processing. STP in the hippocampal CA1 region has been known to require the activation of N-methyl-D-aspartate receptors (NMDARs). The NMDAR dependent hippocampal STP as a potential mechanism for short term memory has been a subject of intense interest for the past few years. Therefore in the present study the effect of oleic acid on NMDAR dependent hippocampal STP was determined in mouse hippocampal slices (in vitro) using Multi-electrode array system. STP was induced by weak tetanic Stimulation (one train of 100 Hz stimulations for 0.1s) of the Schaffer collaterals of CA1 region of the hippocampus in slices treated with different concentrations of oleic acid in presence or absence of NMDAR antagonist D-AP5 (30 µM) . Oleic acid at 20 (mean increase in fEPSP amplitude = ~135 % Vs. Control = 100%; P<0.001) and 30 µM (mean increase in fEPSP amplitude = ~ 280% Vs. Control = 100%); P<0.001) significantly enhanced the STP following weak tetanic stimulation. Lower oleic acid concentrations at 10 µM did not modify the hippocampal STP induced by weak tetanic stimulation. The hippocampal STP induced by weak tetanic stimulation was completely blocked by the NMDA receptor antagonist D-AP5 (30µM) in both oleic acid and control treated hippocampal slices. This lead to the conclusion that the hippocampal STP elicited by weak tetanic stimulation and enhanced by oleic acid was NMDAR dependent. Together these findings suggest that oleic acid may enhance the short term memory and neuronal information processing through the modulation of NMDAR dependent hippocampal short-term synaptic plasticity. In conclusion this study suggests the possible role of oleic acid to prevent the short term memory loss and impaired neuronal function throughout development.

Keywords: oleic acid, short-term potentiation, memory, field excitatory post synaptic potentials, NMDA receptor

Procedia PDF Downloads 335

Authors: Krisztina Bohacs, Klaudia Markus

Abstract:

To author’s best knowledge we are in absence of studies on cognitive program evaluation and we are certainly short of programs that prove to have high effect sizes with strong retention results. The purpose of our study was to investigate the effectiveness of a comprehensive cognitive training program, namely BrainRx. This cognitive rehabilitation program target and remediate seven core cognitive skills and related systems of sub-skills through repeated engagement in game-like mental procedures delivered one-on-one by a clinician, supplemented by digital training. A larger sample of children with learning disability were given pretest and post-test cognitive assessments. The experimental group completed a twenty-week cognitive training program in a BrainRx center. A matched control group received another twenty-week intervention with Feuerstein’s Instrumental Enrichment programs. A second matched control group did not receive training. As for pre- and post-test, we used a general intelligence test to assess IQ and a computer-based test battery for assessing cognition across the lifespan. Multiple regression analyses indicated that the experimental BrainRx treatment group had statistically significant higher outcomes in attention, working memory, processing speed, logic and reasoning, auditory processing, visual processing and long-term memory compared to the non-treatment control group with very large effect sizes. With the exception of logic and reasoning, the BrainRx treatment group realized significantly greater gains in six of the above given seven cognitive measures compared to the Feuerstein control group. Our one-year retention measures showed that all the cognitive training gains were above ninety percent with the greatest retention skills in visual processing, auditory processing, logic, and reasoning. The BrainRx program may be an effective tool to establish long-term cognitive changes in case of students with learning disabilities. Recommendations are made for treatment centers and special education institutions on the cognitive training of students with special needs. The importance of our study is that targeted, systematic, progressively loaded and intensive brain training approach may significantly change learning disabilities.

Keywords: cognitive rehabilitation training, cognitive skills, learning disability, permanent structural cognitive changes

Procedia PDF Downloads 202

Authors: Cory B. Lord

Abstract:

Falls among the elderly population has become an area of concern in healthcare today. The negative impacts of falls lead to increased morbidity, mortality, and financial burdens for both patients and healthcare systems. Falls in the United States is reported at an annual rate of 36 million in those aged 65 and older. Each year, one out of four people in this age group will suffer a fall, with 20% of these falls causing injury. The setting for this Doctor of Nursing Practice (DNP) project was a memory care unit in an assisted living community, as these facilities house cognitively impaired older adults. These communities lack fall prevention programs; therefore, the need exists to add to the body of knowledge to positively impact this population. The objective of this project was to reduce fall rates through the implementation of the Center for Disease Control and Prevention (CDC) STEADI (stopping elderly accidents, deaths, and injuries) program. The DNP project performed was a quality improvement pilot study with a pre and post-test design. This program was implemented in the memory care setting over 12 weeks. The project included an educational session for staff and a fall risk assessment with appropriate resident referrals. The three aims of the DNP project were to reduce fall rates among the elderly aged 65 and older who reside in the memory care unit, increase staff knowledge of STEADI fall prevention measures after an educational session, and assess the willingness of memory care unit staff to adopt an evidence-based a fall prevention program. The Donabedian model was used as a guiding conceptual framework for this quality improvement pilot study. The fall rate data for 12 months before the intervention was evaluated and compared to post-intervention fall rates. The educational session comprised of a pre and post-test to assess staff knowledge of the fall prevention program and the willingness of staff to adopt the fall prevention program. The overarching goal was to reduce falls in the elderly population who live in memory care units. The results of the study showed, on average that the fall rate during the implementation period of STEADI (μ=6.79) was significantly lower when compared to the prior 12 months (μ= 9.50) (p=0.02, α = 0.05). The mean staff knowledge scores improved from pretest (μ=77.74%) to post-test (μ=87.42%) (p=0.00, α= 0.05) after the education session. The results of the willingness to adopt a fall prevention program were scored at 100%. In summation, implementing the STEADI fall prevention program can assist in reducing fall rates for residents aged 65 and older who reside in a memory care setting.

Keywords: dementia, elderly, falls, STEADI

Procedia PDF Downloads 129

Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

Abstract:

Objective: Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioural deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani pomegranate extract on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). Methods: The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 4% pomegranate. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analysed. Results: APPsw/Tg2576 mice that were fed a standard chow diet without pomegranates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, APPsw/Tg2576 mice that were fed a diet containing 4% pomegranates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Conclusion: Our results suggest that dietary supplementation with pomegranates may slow the progression of cognitive and behavioural impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, pomegranates, oman, cognitive decline, memory loss, anxiety, inflammation

Procedia PDF Downloads 528

Authors: Syed Asif Hassan, Tabrej Khan

Abstract:

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

Procedia PDF Downloads 256

Authors: A. M. S. S. Amarasiri, A. P. Attanayake, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

Abstract:

Adriamycin (ADR) is an effective anthracyclin antitumor drug, but its clinical use is limited due to renal toxicity. The leaves of Asparagus falcatus (Family: Liliaceae) have been used in the management of renal diseases since antiquity. In the present investigation, the aqueous leaf extract of A. falcatus was evaluated for acute nephroprotective activity in ADR induced nephrotoxic rats. Nephrotoxicity was induced in healthy male Wistar rats by intraperitoneal administration of ADR 20 mg/kg. The lyophilized powder of the aqueous refluxed (4h) leaf extract of A. falcatus was administered orally at three selected doses; 200, 400 and 600 mg/kg for three consecutive days. Fosinopril sodium (0.09 mg/kg) was used as the standard drug. Administration of the plant extract and the standard drug was commenced 24 hours after the induction of nephrotoxicity to rats. The nephroprotective effect was determined by selected biochemical parameters and by the assessment of histopathology on H and E stained kidney sections. The results were compared to a group of control rats with ADR induced nephrotoxicity. A group of rats administered with the equivalent volume of normal saline served as the healthy control. Administration of ADR 20 mg/kg produced a significant increase in the concentrations of serum creatinine (61%) and urine protein (73%) followed by a significant decrease in serum total protein (21%) and albumin (44%) of the plant extract treated animals compared to the healthy control group (p < 0.05). The aqueous extract of Asparagus falcatus at the three doses; 200, 400 and 600 mg/kg and the standard drug were found to decrease the elevation of concentrations of serum creatinine (33%, 51%, 54% and 42%) and urine protein (8%, 63%, 80% and 86%) respectively. The serum concentrations of total protein (12%, 17%, 29% and 12%) and albumin (3%, 17%, 17% and 16%) were significantly increased compared to the nephrotoxic control group respectively. Assessment of histopathology on H and E stained kidney sections demonstrated that ADR induced renal injury, as evidenced by loss of brush border, cytoplasmic vacuolization, pyknosis in renal tubular epithelial cells, haemorrhages, glomerular congestion and presence of hyaline casts. Treatment with the plant extract and the standard drug resulted in attenuation of the morphological destruction in rats. The results of the present study revealed that the aqueous leaf extract of A. falcatus possesses significant nephroprotective activity against adriamycin induced acute nephrotoxicity. The improved kidney functions were supported with the results of selected biochemical parameters and histological changes observed on H and E stained sections of the kidney tissues in Wistar rats.

Keywords: adriamycin induced nephrotoxicity, asparagus falcatus, biochemical assessment, histopathological assessment, nephroprotective activity

Procedia PDF Downloads 164

Authors: Said S. Almaiuof

Abstract:

Integration Program Through Physical Education Lessons for The Influence of Some Physical Fitness Health-Related Components in Visual Handicapped Children. Propose of the study: The aim of this study is to design and evaluate a program for the physical education lesson to improve the cardio-respiratory endurance, considering the lesson of physical education as one of the educational means to achieve the society aims toward health and fitness, concerning the importance of the cardio-respiratory endurance as an essential one of the physical fitness health-related components. And this program tried to give them hand of help as a part of the society having the same rights as the rest of the society. Methodology: The researcher used the experimental method as a suitable method for this study and tested its hypothesis. The subject of the research selected randomly of the two classes from primary education in TRIPOLI-LIBYA, it was 28 boys (14-15) years old, then divided into groups, experimental group, n=13, which practiced the special exercises program and control group, n=15, which only practiced the normal school program. The selected child subjected to a medical examination in order to make sure that they are healthy, and the Vo2max measured by cycle ergometry and test some physical fitness makers before and after the program. Results: The study cleared that the experimental group developed in all physical variation in comparison with the control group which has a little development in a general balance only. Results are following: 1. The experimental group was successful more than the control group in all the research variation. 2. There were some improvements in time of keeping Balance in control group only. Discussion /conclusion: According to statistical analysis of data related to the values of the variables in this study; the suggested exercise program according to development the cardio respiratory endurance (CRE), and some physical fitness more than the program which already implemented in the school was less effective, just there is developing on keep balancing. It’s statistically significant (p<0.05) after applying this program. Improving the experimental group on (CRE), balance, running, sit and reach, from the suggested exercise program of what indicate the partaking program positive in improve those physical variables, and the selected exercises may contributed in improving the (CRE) for visual impairment and its pivotal in visual impairment children’s life. A health-related physical education curriculum can provide students with substantially more physical activity during physical education classes. The results show that the physical rehabilitation program for visual impairment children helped them in developing their defects due to the injury which means that this program should be in every organization having this part of people to increase their production and give them hand of help as a part of the society having the same rights as the rest of the society and to establish the idea of sport for all.

Keywords: visual handicapped, cardio-respiratory endurance, health, ergometry, education

Procedia PDF Downloads 435

Authors: Tin Yee Ling, Kavita Maravar, Ruzica Ardalic

Abstract:

Background: Uterine torsion (UT) in pregnancy of more than 45-degree along the longitudinal axis is a rare occurrence, and the aetiology remains unclear. Case: A 34-year-old G2P1 woman with a history of one previous caesarean section presented at 36+2 weeks with sudden onset lower abdominal pain, syncopal episode, and tender abdomen on examination. She was otherwise haemodynamically stable. Cardiotocography showed a pathological trace with initial prolonged bradycardia followed by a subsequent tachycardia with reduced variability. An initial diagnosis of uterine dehiscence was made, given the history and clinical presentation. She underwent an emergency caesarean section which revealed a 180-degree UT along the longitudinal axis, with oedematous left round ligament lying transverse anterior to the uterus and a segment of large bowel inferior to the round ligament. Detorsion of uterus was performed prior to delivery of the foetus, and anterior uterine wall was intact with no signs of rupture. There were no anatomical uterine abnormalities found other than stretched left ovarian and round ligaments, which were repaired. Delivery was otherwise uneventful, and she was discharged on day 2 postpartum. Discussion: UT is rare as the number of reported cases is within the few hundreds worldwide. Generally, the uterus is supported in place by uterine ligaments, which limit the mobility of the structure. The causes of UT are unknown, but risk factors such as uterine abnormalities, increased uterine ligaments’ flexibility in pregnancy, and foetal malposition has been identified. UT causes occlusion of uterine vessels, which can lead to ischaemic injury of the placenta causing premature separation of the placenta, preterm labour, and foetal morbidity and mortality if delivery is delayed. Diagnosing UT clinically is difficult as most women present with symptoms similar to placenta abruption or uterine rupture (abdominal pain, vaginal bleeding, shock), and one-third are asymptomatic. The management of UT involves surgical detorsion of the uterus and delivery of foetus via caesarean section. Extra vigilance should be taken to identify the anatomy of the uterus experiencing torsion prior to hysterotomy. There have been a few cases reported with hysterotomy on posterior uterine wall for delivery of foetus as it may be difficult to identify and reverse a gravid UT when foetal well-being is at stake. Conclusion: UT should be considered a differential diagnosis of acute abdominal pain in pregnancy. It is crucial that the torsion is addressed immediately as it is associated with maternal and foetal morbidity and mortality.

Keywords: uterine torsion, pregnancy complication, abdominal pain, torted uterus

Procedia PDF Downloads 161

Authors: Lalita Subedi, Jae Kyoung Chae, Yong Un Park, Cho Kyo Hee, Lee Jae Hyuk, Kang Min Cheol, Sun Yeou Kim

Abstract:

Neuroinflammation may mediate the relationship between low levels of estrogens and neurodegenerative disease. Estrogens are neuroprotective and anti-inflammatory in neurodegenerative disease models. Due to the long term side effects of estrogens, researches have been focused on finding an effective phytoestrogens for biological activities. Daidzein present in soybeans and its active metabolite equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) bears strong antioxidant and anticancer showed more potent anti-inflammatory and neuroprotective role in neuroinflammatory model confirmed its in vitro activity with molecular mechanism through NF-κB pathway. Three major CNS cells Microglia (BV-2), Astrocyte (C6), Neuron (N2a) were used to find the effect of equol in inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), MAPKs signaling proteins, apoptosis related proteins by western blot analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Gries method and ELISA, respectively. Cytokines like tumor necrosis factor-α (TNF-α) and IL-6 were also measured in the conditioned medium of LPS activated cells with or without equol. Equol inhibited the NO production, PGE-2 production and expression of COX-2 and iNOS in LPS-stimulated microglial cells at a dose dependent without any cellular toxicity. At the same time Equol also showed promising effect in modulation of MAPK’s and nuclear factor kappa B (NF-κB) expression with significant inhibition of the production of proinflammatory cytokine like interleukin -6 (IL-6), and tumor necrosis factor -α (TNF-α). Additionally, it inhibited the LPS activated microglia-induced neuronal cell death by downregulating the apoptotic phenomenon in neuronal cells. Furthermore, equol increases the production of neurotrophins like NGF and increase the neurite outgrowth as well. In conclusion the natural daidzein metabolite equol are more active than daidzein, which showed a promising effectiveness as an anti-neuroinflammatory and neuroprotective agent via downregulating the LPS stimulated microglial activation and neuronal apoptosis. This work was supported by Brain Korea 21 Plus project and High Value-added Food Technology Development Program 114006-4, Ministry of Agriculture, Food and Rural Affairs.

Keywords: apoptosis, equol, neuroinflammation, phytoestrogen

Procedia PDF Downloads 361

Authors: Felicia N. Obialo, Aliza Wingo, Thomas Wingo

Abstract:

Psychosocial factors such as personality traits and social networks influence cognitive aging and dementia outcomes both positively and negatively. The inherent complexity of these factors makes defining the underlying mechanisms of their influence difficult; however, exploring their interactions affords promise in the field of cognitive aging. The objective of this study was to elucidate some of these interactions by determining the relationship between social network size and dementia outcomes and by determining whether personality traits mediate this relationship. The longitudinal Alzheimer’s Disease (AD) database provided by Rush University’s Religious Orders Study/Memory and Aging Project was utilized to perform retrospective regression and mediation analyses on 3,591 participants. Participants who were cognitively impaired at baseline were excluded, and analyses were adjusted for age, sex, common chronic diseases, and vascular risk factors. Dementia outcome measures included cognitive trajectory, clinical dementia diagnosis, and postmortem beta-amyloid plaque (AB), and neurofibrillary tangle (NT) accumulation. Personality traits included agreeableness (A), conscientiousness (C), extraversion (E), neuroticism (N), and openness (O). The results show a positive correlation between social network size and cognitive trajectory (p-value = 0.004) and a negative relationship between social network size and odds of dementia diagnosis (p = 0.024/ Odds Ratio (OR) = 0.974). Only neuroticism mediates the positive relationship between social network size and cognitive trajectory (p < 2e-16). Agreeableness, extraversion, and neuroticism all mediate the negative relationship between social network size and dementia diagnosis (p=0.098, p=0.054, and p < 2e-16, respectively). All personality traits are independently associated with dementia diagnosis (A: p = 0.016/ OR = 0.959; C: p = 0.000007/ OR = 0.945; E: p = 0.028/ OR = 0.961; N: p = 0.000019/ OR = 1.036; O: p = 0.027/ OR = 0.972). Only conscientiousness and neuroticism are associated with postmortem AD pathologies; specifically, conscientiousness is negatively associated (AB: p = 0.001, NT: p = 0.025) and neuroticism is positively associated with pathologies (AB: p = 0.002, NT: p = 0.002). These results support the study’s objectives, demonstrating that social network size and personality traits are strongly associated with dementia outcomes, particularly the odds of receiving a clinical diagnosis of dementia. Personality traits interact significantly and beneficially with social network size to influence the cognitive trajectory and future dementia diagnosis. These results reinforce previous literature linking social network size to dementia risk and provide novel insight into the differential roles of individual personality traits in cognitive protection.

Keywords: Alzheimer’s disease, cognitive trajectory, personality traits, social network size

Procedia PDF Downloads 127