Search results for: aberrant corneal occlusion

Authors: Pragathi Gurumurthy, Christina Hagen, Patricia Ulloa, Martin A. Koch, Thorsten M. Buzug

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Obstructive sleep apnea (OSA) is a sleep disorder where the patient suffers a disturbed airflow during sleep due to partial or complete occlusion of the pharyngeal airway. Recently, numerical simulations have been used to better understand the mechanism of pharyngeal collapse. However, to gain confidence in the solutions so obtained, an experimental validation is required. Therefore, in this study an experimental validation of computational fluid dynamics (CFD) used for the study of human pharyngeal flow patterns during OSA is performed. A stationary incompressible Navier-Stokes equation solved using the finite element method was used to numerically study the flow patterns in a computed tomography-based human pharynx model. The inlet flow rate was set to 250 ml/s and such that a flat profile was maintained at the inlet. The outlet pressure was set to 0 Pa. The experimental technique used for the validation of CFD of fluid flow patterns is phase contrast-MRI (PC-MRI). Using the same computed tomography data of the human pharynx as in the simulations, a phantom for the experiment was 3 D printed. Glycerol (55.27% weight) in water was used as a test fluid at 25°C. Inflow conditions similar to the CFD study were simulated using an MRI compatible flow pump (CardioFlow-5000MR, Shelley Medical Imaging Technologies). The entire experiment was done on a 3 T MR system (Ingenia, Philips) with 108 channel body coil using an RF-spoiled, gradient echo sequence. A comparison of the axial velocity obtained in the pharynx from the numerical simulations and PC-MRI shows good agreement. The region of jet impingement and recirculation also coincide, therefore validating the numerical simulations. Hence, the experimental validation proves the reliability and correctness of the numerical simulations.

Keywords: computational fluid dynamics, experimental validation, phase contrast-MRI, obstructive sleep apnea

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Authors: Mohd. Ashik Shahrier, Hiromi Wada

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Prenatal ethanol exposure has potential to induce difficulties in the social behavior of rats and can alter pup-dam communication suggesting that deficits in pups could result in altered dam behavior, which in turn could result in more aberrant behavior in the pup. Ultrasonic vocalization (USV) is a sensitive tool for investigating social behavior between rat pups and their dam. Rat pups produce USVs on separation from their dam. This signals the dam to locate her pups and retrieve them back to the nest. In this study, it was predicted that prenatal ethanol exposure cause alterations on the acoustic characteristics of USVs in rat pups. Thirteen pregnant rats were purchased and randomly assigned into three groups: high-ethanol (n = 4), low-ethanol (n = 5), and control (n = 4) groups. Laboratory ethanol (purity = 99.5%) was dissolved in tap water and administered to the high- and low-ethanol groups as drinking water from gestational days (GD) 8-20. Ethanol-containing water was administered to the animals in three stages by gradually increasing the concentration between GDs 8–20. From GDs 8–10, 10% and 5%, from GDs 11–13, 20% and 10%, and from GDs 14–20, 30% and 15% ethanol-containing water (v/v) was administered to the high- and low-ethanol groups, respectively. Tap water without ethanol was given to the control group throughout the experiment. The day of birth of the pups was designated as postnatal day (PND) 0. On PND 4, each litter was culled to four male and four female pups. For the present study, two male and two female pups were randomly sampled from each litter as subjects. Thus, eight male and eight female pups from the high-ethanol and control groups and another 10 male and 10 female pups from the low-ethanol group, were sampled. An ultrasonic microphone and the Sonotrack system version 2.4.0 (Metris, Hoofddorp, The Netherlands) were used to record and analyze USVs of the pups. On postnatal days 4, 8, 12 and 16, the resultant pups were individually isolated from their dams and littermates, and USVs were recorded for 5 min in a sound-proof box. Pups in the high-ethanol group produced greater number of USVs compared with that in both low-ethanol and control groups on PND 12. Rat pups in the high-ethanol group also produced higher mean, minimum, and maximum fundamental frequencies of USVs compared with that in both low-ethanol and control groups. Male pups in the high-ethanol group had higher USV amplitudes than in those in low-ethanol and control groups on PND 12. These results suggest that pups in the high-ethanol group relatively experienced more negative emotionality due to the ethanol-induced neuronal activation in the core limbic system and tegmental structures and accordingly, produced altered USVs as distress calls.

Keywords: emotionality, ethanol, maternal separation, ultrasonic vocalization

Procedia PDF Downloads 104

Authors: Ziwei Song, Junjun Fan, Jeremy Teo, Yang Yu, Yukun Ma, Jie Yan, Shupei Mo, Lisa Tucker-Kellogg, Peter So, Hanry Yu

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Liver is the center of detoxification and exposed to toxic metabolites all the time. It is highly regenerative after injury, with the ability to restore even after 70% partial hepatectomy. Most of the previous studies were using hepatectomy as injury models for liver regeneration study. There is limited understanding of small-scale liver injury, which can be caused by either low dose drug consumption or hepatocyte routine metabolism. Although these small in situ injuries do not cause immediate symptoms, repeated injuries will lead to aberrant wound healing in liver. Therefore, the cellular dynamics during liver regeneration is critical for our understanding of liver regeneration mechanism. We aim to study the liver regeneration of small-scale in situ liver injury in transgenic mice labeling actin (Lifeact-GFP). Previous studies have been using sample sections and biopsies of liver, which lack real-time information. In order to trace every individual hepatocyte during the regeneration process, we have developed and optimized an intravital imaging system that allows in vivo imaging of mouse liver for consecutive 5 days, allowing real-time cellular tracking and quantification of hepatocytes. We used femtosecond-laser ablation to make controlled and repeatable liver injury model, which mimics the real-life small in situ liver injury. This injury model is the first case of its kind for in vivo study on liver. We found that small-scale in situ liver injury is repaired by the coordination of hypertrophy and migration of hepatocytes. Hypertrophy is only transient at initial phase, while migration is the main driving force to complete the regeneration process. From cellular aspect, Akt/mTOR pathway is activated immediately after injury, which leads to transient hepatocyte hypertrophy. From mechano-sensing aspect, the actin cable, formed at apical surface of wound proximal hepatocytes, provides mechanical tension for hepatocyte migration. This study provides important information on both chemical and mechanical signals that promote liver regeneration of small in situ injury. We conclude that hypertrophy and migration play a dominant role at different stages of liver regeneration.

Keywords: hepatocyte, hypertrophy, intravital imaging, liver regeneration, migration

Procedia PDF Downloads 182

Authors: Naim Izet Kajtazi

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Context: Although rare, glomus tumor (i.e., nonchromaffin chemodectomas and paragan¬gliomas) is the most common middle ear tumor, with female predominance. Pre-operative embolization is often required to devascularize the hypervascular tumor for better surgical outcomes. Process: A 35-year-old female presented with episodes of frequent dizziness, ear fullness, and right ear tinnitus for 12 months. Head imaging revealed a right glomus tympanicum tumor. She underwent pre-operative endovascular embolization of the glomus tympanicum tumor with surgical, cyanoacrylate-based glue. Immediately after the procedure, she developed drowsiness and severe pain in the right temporal region. Further investigations revealed a right cerebellar stroke in the posterior inferior cerebellar artery territory. She was treated with intravenous heparin, followed by one year of oral anticoagulation. With rehabilitation, she significantly recovered from her post embolization stroke. However, the tumor was resected at another institution. Ten years later, follow-up imaging indicated a gradual increase in the size of the glomus jugulare tumor, compressing the nearby critical vascular structures. She subsequently received radiation therapy to treat the residual tumor. Outcome: Currently, she has no neurological deficit, but her mild dizziness, right ear tinnitus, and hearing impairment persist. Relevance: This case highlights the complex nature of these tumors, which often bring challenges to the patients as well as treatment teams. The multi-disciplinary team approach is necessary to tailor the management plan for individual tumors. Although embolization is a safe procedure, careful attention and thoughtful anatomic knowledge regarding dangerous anastomosis are essential to avoid devastating complications. Complications occur due to encountered vessel anomalies and new anastomoses formed during the gluing and changes in hemodynamics.

Keywords: stroke, embolization, MRI brain, cerebral angiogram

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Authors: Pavel Damborsky, Martina Zamorova, Jaroslav Katrlik

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Prostate cancer is annually the most common newly diagnosed cancer among men. An extensive number of evidence suggests that traditional serum Prostate-specific antigen (PSA) assay still suffers from a lack of sufficient specificity and sensitivity resulting in vast over-diagnosis and overtreatment. Thus, the early-stage detection of prostate cancer (PCa) plays undisputedly a critical role for successful treatment and improved quality of life. Over the last decade, particular altered glycans have been described that are associated with a range of chronic diseases, including cancer and inflammation. These glycans differences enable a distinction to be made between physiological and pathological state and suggest a valuable biosensing tool for diagnosis and follow-up purposes. Aberrant glycosylation is one of the major characteristics of disease progression. Consequently, the aim of this study was to develop a more reliable tool for early-stage PCa diagnosis employing lectins as glyco-recognition elements. Biosensor and biochip technology putting to use lectin-based glyco-profiling is one of the most promising strategies aimed at providing fast and efficient analysis of glycoproteins. The proof-of-concept experiments based on sandwich assay employing anti-PSA antibody and an aptamer as a capture molecules followed by lectin glycoprofiling were performed. We present a lectin-based biosensing assay for glycoprofiling of serum biomarker PSA using different biosensor and biochip platforms such as label-free surface plasmon resonance (SPR) and microarray with fluorescent label. The results suggest significant differences in interaction of particular lectins with PSA. The antibody-based assay is frequently associated with the sensitivity, reproducibility, and cross-reactivity issues. Aptamers provide remarkable advantages over antibodies due to the nucleic acid origin, stability and no glycosylation. All these data are further step for construction of highly selective, sensitive and reliable sensors for early-stage diagnosis. The experimental set-up also holds promise for the development of comparable assays with other glycosylated disease biomarkers.

Keywords: biomarker, glycosylation, lectin, prostate cancer

Procedia PDF Downloads 379

Authors: M. E. Kolpakova, A. A. Jakovleva, L. S. Poliakova, H. El Amghari, S. Soliman, D. R. Faizullina, V. V. Sharoyko

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Brain neuroplasticity is associated with blood-brain barrier vascular endothelial proteoglycans and post-stroke microglial activation. The study of the mechanisms of reperfusion injury limitation by remote ischemic postconditioning (RC) is of interest due to the effects on functional recovery after cerebral ischemia. The goal of the study is the assessment of the role of syndecan-1 (SDC-1) in restriction of ischemic-reperfusion injury on middle cerebral artery model in rats using RC protocol. Randomized controlled trials were conducted. Ischemia was performed by middle cerebral artery occlusion by Belayev L. (1996) on the Wistar rat-males (n= 87) weighting 250 ± 50 g. under general anesthesia (Zoletil 100 и Xylazine 2%). Syndecan-1 (SDC-1) concentration difference in plasma samples of false operated animals and animals with brain ischemia was 30% (30 min. МСАо: 41.4 * ± 1.3 ng/ml). SDC-1 concentration in animal plasma samples with ischemia + RC protocol was 112% (30 min МСАо+ RC): 67.8**± 5.8 ng/ml). Calculation of infarction volume in the ischemia group revealed brain injury in 31.97 ± 2.5%; the volume of infarction was 13.6 ± 1.3% in 30 min. МCАо + RC group. Swelling of tissue in the group 30 min. МCАо + RC was 16 ± 2.1%; it was 47 ± 3.3%. in 30 min. МCАо group. Correlation analysis showed a high direct correlation relationship between infarct area and muscle strength in the right forelimb (КК=0.72) in the 30 min. МCАо + RC group. Correlation analysis showed very high inverse correlation between infarct area and capillary blood flow in the 30 min. МCАо + RC group (p <0.01; r = -0.98). We believe the SDC-1 molecule in blood plasma may play role of potential messenger of ischemic-reperfusion injury restriction mechanisms. This leads to infarct-limiting effect of remote ischemic postconditioning and early functioning recovery.

Keywords: ischemia, МСАо, remote ischemic postconditioning, syndecan-1

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Authors: Ayda Youssef, Tarek Rafaat, Iman zaky

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Purpose: Langerhans’ cell histiocytosis (LCH) is not uncommon pathology that implies aberrant proliferation of a specific dendritic (Langerhans) cell. These atypical but mature cells of monoclonal origin can infiltrate many sites of the body and may occur as localized lesions or as widespread systemic disease. Liver is one of the uncommon sites of affection. The twofold objective of this study is to illustrate the radiological presentation of this disease, and to compare these results with previously reported series. Methods and Materials: Between 2007 and 2012, 150 patients with biopsy-proven LCH were treated in our hospital, a paediatric cancer tertiary care center. A retrospective review of radiographic images and reports was performed. There were 33 patients with liver affection are stratified. All patients underwent imaging studies, mostly US and CT. A chart review was performed to obtain demographic, clinical and radiological data. They were analyzed and compared to other published series. Results: Retrospective assessment of 150 patients with LCH was performed, among them 33 patients were identified who had liver involvement. All these patients developed multisystemic disease; They were 12 females and 21 males with (n= 32), seven of them had marked hepatomegaly. Diffuse hypodense liver parenchyma was encountered in five cases, the periportal location has a certain predilection in cases of focal affection where three cases has a hypodense periportal soft tissue sheets, one of them associated with dilated biliary radicals, only one case has multiple focal lesions unrelated to portal tracts. On follow up of the patients, two cases show abnormal morphology of liver with bossy outline. Conclusion: LCH is a not infrequent disease. A high-index suspicion should be raised in the context of diagnosis of liver affection. A biopsy is recommended in the presence of radiological suspicion. Chemotherapy is the preferred therapeutic modality. Liver histiocytosis are not disease specific features but should be interpreted in conjunction with the clinical history and the results of biopsy. Clinical Relevance/Application: Radiologist should be aware of different patterns of hepatobiliary histiocytosis, Thus early diagnosis and proper management of patient can be conducted.

Keywords: langerhans’ cell histiocytosis, liver, medical and health sciences, radiology

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Authors: Mahboubeh Kabiri, Saba Aslani

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Among various approaches used for the treatment of cardiovascular diseases, the occlusion of the small-diameter vascular graft (SDVG) is still an unresolved problem which seeks further research to address them. Though autografts are now the gold standards to be replaced for blocked coronary arteries, they suffer from inadequate quality and quantity. On the other hand, the major problems of the tissue engineered grafts are thrombosis and intimal hyperplasia. Provision of a suitable spatiotemporal release pattern of anticoagulant agents such as heparin and aspirin can be a step forward to overcome such issues . Herein, we fabricated electrospun scaffolds from FDA (Food and Drug Administration) approved poly-L-lactic acid (PLLA) with aspirin loaded into the nanofibers. Also, we surface coated the scaffolds with Amniotic Membrane lysate as a source for natural elastic polymers and a mimic of endothelial basement membrane. The scaffolds were characterized thoroughly structurally and mechanically for their morphology, fiber orientation, tensile strength, hydrophilicity, cytotoxicity, aspirin release and cell attachment support. According to the scanning electron microscopy (SEM) images, the size of fibers ranged from 250 to 500 nm. The scaffolds showed appropriate tensile strength expected for vascular grafts. Cellular attachment, growth, and infiltration were proved using SEM and MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. Drug-loaded scaffolds showed a sustained release profile of aspirin in 7 days. An enhanced cytocompatibility was observed in AM-coated electrospun PLLA fibers compared to uncoated scaffolds. Our results together indicated that AM lysate coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.

Keywords: vascular tissue engineering, vascular grafts, anticoagulant agent, aspirin, amniotic membrane

Procedia PDF Downloads 135

Authors: Raquel Galante, Marina Braga, Daniela Ghisleni, Terezinha J. A. Pinto, Rogério Colaço, Ana Paula Serro

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The sensitive nature of soft biomaterials, such as hydrogels, renders their sterilization a particularly challenging task for the biomedical industry. Widely used contact lenses are now studied as promising platforms for topical corneal drug delivery. However, to the best of the authors knowledge, the influence of sterilization methods on these systems has yet to be evaluated. The main goal of this study was to understand how different pairs drug-hydrogel would interact under an ozone-based sterilization method in comparison with two conventional processes (steam heat and gamma irradiation). For that, Si-Hy containing hydroxylethyl methacrylate (HEMA) and [tris(trimethylsiloxy)silyl]propyl methacrylate (TRIS) was produced and soaked in different drug solutions, commonly used for the treatment of ocular diseases (levofloxacin, chlorhexidine, diclofenac and timolol maleate). The drug release profiles and main material properties were evaluated before and after the sterilization. Namely, swelling capacity was determined by water uptake studies, transparency was accessed by UV-Vis spectroscopy, surface topography/morphology by scanning electron microscopy (SEM) and mechanical properties by performing tensile tests. The drug released was quantified by high performance liquid chromatography (HPLC). The effectiveness of the sterilization procedures was assured by performing sterility tests. Ozone gas method led to a significant reduction of drug released and to the formation of degradation products specially for diclofenac and levofloxacin. Gamma irradiation led to darkening of the loaded Si-Hys and to the complete degradation of levofloxacin. Steam heat led to smoother surfaces and to a decrease of the amount of drug released, however, with no formation of degradation products. This difference in the total drug released could be the related to drug/polymer interactions promoted by the sterilization conditions in presence of the drug. Our findings offer important insights that, in turn, could be a useful contribution to the safe development of actual products.

Keywords: drug delivery, silicone hydrogels, sterilization, gamma irradiation, steam heat, ozone gas

Procedia PDF Downloads 285

Authors: Noorulain Khalid, Unsaar Hayat, Muhammad Chaudhary, Christos Iosifidis, Felipe Dhawahir-Scala, Fiona Carley

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Dry eye disease (DED) is a common condition seen in the emergency eye department (EED) at Manchester Royal Eye Hospital (MREH). However, there is variability in the prescription of lubricating eye drops among different healthcare providers. The aim of this study was to develop an up-to-date, standardized algorithm for the prescription of lubricating eye drops in the EED at MREH based on international and national guidelines. The study also aimed to assess the impact of implementing the guideline on the rate of inappropriate lubricant prescriptions. Primarily, the impact was to be assessed in the form of the appropriateness of prescriptions for patients’ DED. The impact was secondary to be assessed through analysis of the cost to the hospital. Data from 845 patients who attended the EED over a 3-month period were analyzed, and 157 patients met the inclusion and exclusion criteria. After conducting a review of the literature and collaborating with the corneal team, an algorithm for the prescription of lubricants in the EED was developed. Three plan-do-study-act (PDSA) cycles were conducted, with interventions such as emails, posters, in-person reminders, and education for incoming trainees. The appropriateness of prescriptions was evaluated against the guidelines. Data were collected from patient records and analyzed using statistical methods. The appropriateness of prescriptions was assessed by comparing them to the guidelines and by clinical correlation with a specialized registrar. The study found a substantial improvement in the number of appropriate prescriptions, with an increase from 55% to 93% over the three PDSA cycles. There was additionally a 51% reduction in expenditure on lubricant prescriptions, resulting in cost savings for the hospital (approximate saving of £50/week). Theoretical importance: Appropriate prescription of lubricating eye drops improves disease management for patients and reduces costs for the hospital. The development and implementation of a standardized guideline facilitate the achievement of these goals. Conclusion: This study highlights the inconsistent management of DED in the EED and the potential lack of training in this area for healthcare providers. The implementation of a standardized, easy-to-follow guideline for lubricating eye drops can help to improve disease management while also resulting in cost savings for the hospital.

Keywords: lubrication, dry eye disease, guideline, prescription

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Authors: Preethy Mary Donald, Renjith George

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Oral tori are localized non-neoplastic protuberances of maxilla and mandible. Torus palatinus (TP) is found on the midline of the roof of mouth existing as single growth or in clusters. Torus mandibularis(TM) is located on the lingual aspect of the mandible commonly between canine and premolar region. Etiology of their presence was not clear and was found to be multifactorial. Their variations in relation to age, gender, ethnicity and also the characteristics of TP and TM have become the interest of multiple studies. The objectives of this study were to determine the prevalence of torus palatinus (TP) and torus mandibularis (TM) among patients who have visited outpatient department, Faculty of Dentistry, Melaka Manipal Medical College. 108 patients were examined for the presence of oral tori at the outpatient department, Faculty of Dentistry, Melaka-Manipal Medical College. Factors such as age, gender, ethnicity of the patients and size, shape, location of the oral tori were studied. For TP, Malays (62.96%) have been found to have the highest prevalence than Chinese (43.3%) and Indians (35.71%). For TM, Chinese (7.46%) had predominated compared to Malays (7.41%) and Indians (0%). There is no significant association between occurrence of TP and TM with age, gender and ethnicity. For Torus palatinus, the most common size was Grade 1(1-3mm), most common location was molar region, and the most common shape was spindle. For Torus mandibularis, the most frequent location was canine premolar region and exists in unilateral single or bilateral single fashion. The overall prevalence rates were 47.2% for TP and 6.48% for TM. However, there is no significant association between occurrence of TP and TM with age, gender and ethnicity. The results showed variations in clinical characteristics and support the findings that occurrence of tori is a dynamic phenomenon which is multifactorial owing to the environmental factors such as stress from occlusion and dietary habits. It could be due to the genetic make-up of the individual.

Keywords: torus palatinus, torus mandibularis, age, gender

Procedia PDF Downloads 250

Authors: Adebisi Adunola Demehin, Wanlaya Thamnarak, Jaruwan Chatwichien, Chatchakorn Eurtivong, Kiattawee Choowongkomon, Somsak Ruchirawat, Nopporn Thasana

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The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein involved in cellular signalling processes and, its aberrant activity is crucial in the development of many cancers such as lung cancer. Selaginellaceae are fern allies that have long been used in Chinese traditional medicine to treat various cancer types, especially lung cancer. Biflavonoids, the major secondary metabolites in Selaginellaceae, have numerous pharmacological activities, including anti-cancer and anti-inflammatory. For instance, amentoflavone induces a cytotoxic effect in the human NSCLC cell line via the inhibition of PARP-1. However, to the best of our knowledge, there are no studies on biflavonoids as EGFR inhibitors. Thus, this study aims to investigate the EGFR inhibitory activities of biflavonoids isolated from Selaginella siamensis and Selaginella bryopteris. Amentoflavone, tetrahydroamentoflavone, sciadopitysin, robustaflavone, robustaflavone-4-methylether, delicaflavone, and chrysocauloflavone were isolated from the ethyl-acetate extract of the whole plants. The structures were determined using NMR spectroscopy and mass spectrometry. In vitro study was conducted to evaluate their cytotoxicity against A549, HEPG2, and T47D human cancer cell lines using the MTT assay. In addition, a target-based assay was performed to investigate their EGFR inhibitory activity using the kinase inhibition assay. Finally, a molecular docking study was conducted to predict the binding modes of the compounds. Robustaflavone-4-methylether and delicaflavone showed the best cytotoxic activity on all the cell lines with IC50 (µM) values of 18.9 ± 2.1 and 22.7 ± 3.3 on A549, respectively. Of these biflavonoids, delicaflavone showed the most potent EGFR inhibitory activity with an 84% relative inhibition at 0.02 nM using erlotinib as a positive control. Robustaflavone-4-methylether showed a 78% inhibition at 0.15 nM. The docking scores obtained from the molecular docking study correlated with the kinase inhibition assay. Robustaflavone-4-methylether and delicaflavone had a docking score of 72.0 and 86.5, respectively. The inhibitory activity of delicaflavone seemed to be linked with the C2”=C3” and 3-O-4”’ linkage pattern. Thus, this study suggests that the structural features of these compounds could serve as a basis for developing new EGFR-TK inhibitors.

Keywords: anticancer, biflavonoids, EGFR, molecular docking, Selaginellaceae

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Authors: Syed Dawood Md. Taimur, Md. Hasanur Rahman, Syeda Fahmida Afrin, Farzana Islam

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The concept of myocardial injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. In recent years, percutaneous coronary intervention (PCI) has become a well-established technique for the treatment of coronary artery disease. PCI improves symptoms in patients with coronary artery disease and it has been increasing the safety of procedures. However, peri- and post-procedural myocardial injury, including angiographical slow coronary flow, microvascular embolization, and elevated levels of cardiac enzyme, such as creatine kinase and troponin-T and -I, has also been reported even in elective cases. Furthermore, myocardial reperfusion injury at the beginning of myocardial reperfusion, which causes tissue damage and cardiac dysfunction, may occur in cases of the acute coronary syndrome. Because patients with myocardial injury is related to larger myocardial infarction and have a worse long-term prognosis than those without myocardial injury, it is important to prevent myocardial injury during and/or after PCI in patients with coronary artery disease. To date, many studies have demonstrated that adjunctive pharmacological treatment suppresses myocardial injury and increases coronary blood flow during PCI procedures. In this review, we highlight the usefulness of pharmacological treatment in combination with PCI in attenuating myocardial injury in patients with coronary artery disease.

Keywords: coronary artery disease, percutaneous coronary intervention, myocardial injury, pharmacology

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Authors: Cytha Nilam Chairani, Ditha Noviantika, Hidayati Amir, Nurul Khairiyah, Siti Rahmadita, Fadila Khairani

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Background: Dental caries is one of the most common diseases with high prevalence in children. The first permanent molar (FPM) has an essential role in establishing the occlusion. Nevertheless, FPM is very prone to caries because of various factors, such as their anatomical structure and early emergence in oral cavity. It is due to the little knowledge from parents and children regarding the timing of emergence of FPM in oral cavity which is still considered as primary teeth. Furthermore, the lack of knowledge from parents and children may affect their oral hygiene practice resulting to carious process. Objective: The aim of this study was to assess the status of FPM caries and its association with children’s oral hygiene practice in 9-12-year-old school children in Lubuk Kilangan Community Health Centre, Padang City. Methods: A cross-sectional study was performed in 50 school children (9-12 years old) using random sampling technique from two randomly selected schools in Lubuk Kilangan Community Health Centre, Padang City. A questionnaire was developed from other studies consisting of four closed ended questions regarding oral health practice. The data obtained were analyzed statistically using Mann-Whitney Test to assess the status of FPM caries and its association with children’s oral hygiene practice. Results: The results showed that 32% of children had FPMs sound and the remaining 68% had FPMs carious which were grouped into 1-2 FPMs carious (60%) and 3-4 FPMs carious (8%). The caries status of mandibular FPM (64%) was higher compared to maxillary FPM (10%). Conclusion: There was significant association in subject who did not visit dentist in the last 6 months which had more carious FPMs compared to subject who visited dentist (p < 0.05). There was no significant association between the status of FPM caries and knowledge of the timing eruption of FPM, oral hygiene instruction from parents and tooth brushing (p > 0.05).

Keywords: dental caries, children, first permanent molar, oral hygiene practice

Procedia PDF Downloads 247

Authors: Fae Princess Bermudez

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Background: One of the least significant leads on a 12-lead electrocardiogram is the augmented right lead (aVR), as it is not as specific compared to the other leads. In this case series, the value of lead aVR, which is more often than not ignored, is highlighted. Three cases of aVR ST segment elevation on 12-lead electrocardiogram are described, with the end outcome of demise of all three patients. The importance of immediate revascularization is described to improve prognosis in this group of patients. Objectives: This case series aims to primarily present under-reported cases of isolated aVR ST-segrment elevation myocardial infarction (STEMI), their course and outcome. More specific aims are to identify the criteria in determination of isolated aVR STEMI, know its clinical significance, and determine appropriate management for patients with this ECG finding. Method: A short review of previous studies, case reports, articles and guidelines from 2011-2016 was done. The author reviewed available literature, sorted out those that proved to be significant for the presented cases, and described them in conjunction with the aforementioned cases. Findings: Based on the limited information on these rare or under-reported cases, it was found that isolated aVR STEMI had a poorer prognosis that led to significant mortality and morbidity of patients. The significance of aVR ST-elevation was that of an occlusion of the left coronary artery or a severe three-vessel disease in the presence of an Acute Coronary Syndrome. Guidelines from American Heart Association/American College of Cardiology Foundation in 2013 already recognized ST-elevation of lead aVR in isolation as a STEMI; hence, recommended that patients with this particular ECG finding should undergo reperfusion strategies to improve prognosis. Conclusion: The indispensability of isolated aVR ST-segment elevation on ECG should alert physicians, especially Emergency physicians, to the high probability of Acute Coronary Syndrome with a very poor prognosis. If this group of patients is not promptly managed, demise may ensue, with cardiogenic shock as the most probable cause. With this electrocardiogram finding, physicians must be quick to make clinical decisions to increase chances of survival of this group of patients.

Keywords: AVR ST-elevation, diffuse ST-segment depression, left coronary artery infarction, myocardial infarction

Procedia PDF Downloads 183

Authors: Anoop T. R., Otman Basir, Robert F. Hess, Eileen E. Birch, Brooke A. Koritala, Reed M. Jost, Becky Luu, David Stager, Ben Thompson

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Strabismus refers to a misalignment of the eyes. Early detection and treatment of strabismus in childhood can prevent the development of permanent vision loss due to abnormal development of visual brain areas. We developed a two-stage method for strabismus detection and classification based on photographs of the face. The first stage detects the presence or absence of strabismus, and the second stage classifies the type of strabismus. The first stage comprises face detection using Haar cascade, facial landmark estimation, face alignment, aligned face landmark detection, segmentation of the eye region, and detection of strabismus using VGG 16 convolution neural networks. Face alignment transforms the face to a canonical pose to ensure consistency in subsequent analysis. Using facial landmarks, the eye region is segmented from the aligned face and fed into a VGG 16 CNN model, which has been trained to classify strabismus. The CNN determines whether strabismus is present and classifies the type of strabismus (exotropia, esotropia, and vertical deviation). If stage 1 detects strabismus, the eye region image is fed into stage 2, which starts with the estimation of pupil center coordinates using mask R-CNN deep neural networks. Then, the distance between the pupil coordinates and eye landmarks is calculated along with the angle that the pupil coordinates make with the horizontal and vertical axis. The distance and angle information is used to characterize the degree and direction of the strabismic eye misalignment. This model was tested on 100 clinically labeled images of children with (n = 50) and without (n = 50) strabismus. The True Positive Rate (TPR) and False Positive Rate (FPR) of the first stage were 94% and 6% respectively. The classification stage has produced a TPR of 94.73%, 94.44%, and 100% for esotropia, exotropia, and vertical deviations, respectively. This method also had an FPR of 5.26%, 5.55%, and 0% for esotropia, exotropia, and vertical deviation, respectively. The addition of one more feature related to the location of corneal light reflections may reduce the FPR, which was primarily due to children with pseudo-strabismus (the appearance of strabismus due to a wide nasal bridge or skin folds on the nasal side of the eyes).

Keywords: strabismus, deep neural networks, face detection, facial landmarks, face alignment, segmentation, VGG 16, mask R-CNN, pupil coordinates, angle deviation, horizontal and vertical deviation

Procedia PDF Downloads 56

Authors: Zou Xuan, Liu Hongchen

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The ideal dentin desensitizing agent should not only have good biological safety, simple clinical operation mode, the superior treatment effect, but also should have a durable effect to resist the oral environmental temperature change and oral mechanical abrasion, so as to achieve a persistent desensitization effect. Also, when using desensitizing agent to prevent the post-operative hypersensitivity, we should not only prevent it from affecting crowns’ retention, but must understand its effects on bond strength of dentin adhesives. There are various of desensitizers and dentin adhesives in clinical treatment. They have different chemical or physical properties. Whether the use of desensitizing agent would affect the bond strength of dentin adhesives still need further research. In this in vitro study, we built the hypersensitive dentin model and post-operative dentin model, to evaluate the sealing effects and durability on exposed tubule by three different dentin desensitizers and to evaluate the sealing effects and the bond strength of dentin adhesives after using three different dentin desensitizers on post-operative dentin. The result of this study could provide some important references for clinical use of dentin desensitizing agent. 1. As to the three desensitizers, the hypersensitive dentin model was built to evaluate their sealing effects on exposed tubule by SEM observation and dentin permeability analysis. All of them could significantly reduce the dentin permeability. 2. Test specimens of three groups treated by desensitizers were subjected to aging treatment with 5000 times thermal cycling and toothbrush abrasion, and then dentin permeability was measured to evaluate the sealing durability of these three desensitizers on exposed tubule. The sealing durability of three groups were different. 3. The post-operative dentin model was built to evaluate the sealing effects of the three desensitizers on post-operative dentin by SEM and methylene blue. All of three desensitizers could reduce the dentin permeability significantly. 4. The influences of three desensitizers on the bonding efficiency of total-etch and self-etch adhesives were evaluated with the micro-tensile bond strength study and bond interface morphology observation. The dentin bond strength for Green or group was significantly lower than the other two groups (P<0.05).

Keywords: dentin, desensitizer, dentin permeability, thermal cycling, micro-tensile bond strength

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Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam

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The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.

Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin

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Authors: Manami Masuda, Mariko Era, Takayoshi Kawahara, Takahide Kanyama, Hiroshi Morita

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Objectives: Fatty acid salts are a type of anionic surfactant and are produced from fatty acids and alkali. Moreover, fatty acid salts are known to have potent antibacterial activities. Acanthamoeba is ubiquitously distributed in the environment including sea water, fresh water, soil and even from the air. Although generally free-living, Acanthamoeba can be an opportunistic pathogen, which could cause a potentially blinding corneal infection known as Acanthamoeba keratitis. So, in this study, we evaluated the anti-amoeba activity of fatty acid salts and fatty acids to Acanthamoeba castellanii ATCC 30010. Materials and Methods: The antibacterial activity of 9 fatty acid salts (potassium butyrate (C4K), caproate (C6K), caprylate (C8K), caprate (C10K), laurate (C12K), myristate (C14K), oleate (C18:1K), linoleate (C18:2K), linolenate (C18:3K)) tested on cells of Acanthamoeba castellanii ATCC 30010. Fatty acid salts (concentration of 175 mM and pH 10.5) were prepared by mixing the fatty acid with the appropriate amount of KOH. The amoeba suspension mixed with KOH with a pH adjusted solution was used as the control. Fatty acids (concentration of 175 mM) were prepared by mixing the fatty acid with Tween 80 (20 %). The amoeba suspension mixed with Tween 80 (20 %) was used as the control. The anti-amoeba method, the amoeba suspension (3.0 × 104 cells/ml trophozoites) was mixed with the sample of fatty acid potassium (final concentration of 175 mM). Samples were incubated at 30°C, for 10 min, 60 min, and 180 min and then the viability of A. castellanii was evaluated using plankton counting chamber and trypan blue stainings. The minimum inhibitory concentration (MIC) against Acanthamoeba was determined using the two-fold dilution method. The MIC was defined as the minimal anti-amoeba concentration that inhibited visible amoeba growth following incubation (180 min). Results: C8K, C10K, and C12K were the anti-amoeba effect of 4 log-unit (99.99 % growth suppression of A. castellanii) incubated time for 180 min against A. castellanii at 175mM. After the amoeba, the suspension was mixed with C10K or C12K, destroying the cell membrane had been observed. Whereas, the pH adjusted control solution did not exhibit any effect even after 180 min of incubation with A. castellanii. Moreover, C6, C8, and C18:3 were the anti-amoeba effect of 4 log-unit incubated time for 60 min. C4 and C18:2 exhibited a 4-log reduction after 180 min incubation. Furthermore, the minimum inhibitory concentration (MIC) was determined. The MIC of C10K, C12K and C4 were 2.7 mM. These results indicate that C10K, C12K and C4 have high anti-amoeba activity against A. castellanii and suggest C10K, C12K and C4 have great potential for antimi-amoeba agents.

Keywords: Fatty acid salts, anti-amoeba activities, Acanthamoeba, fatty acids

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Authors: Jae-Yong Park, Yeo-Kyeong Lee, Hee-Sun Kim

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Purpose: This study aims at investigating the mechanical behaviors of mastication, according to various teeth movement. There are three masticatory cases which are general case and 2 cases of teeth movement. General case includes the common arrange of all teeth and 2 cases of teeth movement are that one is the half movement location case of molar teeth in no. 14 tooth seat after extraction of no. 14 tooth and the other is no. 14 tooth seat location case of molar teeth after extraction in the same case before. Materials and Methods: In order to analyze these cases, 3 dimensional finite element (FE) model of the skull were generated based on computed tomography images, 964 dicom files of 38 year old male having normal occlusion status. An FE model in general occlusal case was used to develop CAE procedure. This procedure was applied to FE models in other occlusal cases. The displacement controls according to loading condition were applied effectively to simulate occlusal behaviors in all cases. From the FE analyses, von Mises stress distribution of skull and teeth was observed. The von Mises stress, effective stress, had been widely used to determine the absolute stress value, regardless of stress direction and yield characteristics of materials. Results: High stress was distributed over the periodontal area of mandible under molar teeth when the mandible was transmitted to the coronal-apical direction in the general occlusal case. According to the stress propagation from teeth to cranium, stress distribution decreased as the distribution propagated from molar teeth to infratemporal crest of the greater wing of the sphenoid bone and lateral pterygoid plate in general case. In 2 cases of teeth movement, there were observed that high stresses were distributed over the periodontal area of mandible under teeth where they are located under the moved molar teeth in cranium. Conclusion: The predictions of the mechanical behaviors of general case and 2 cases of teeth movement during the masticatory process were investigated including qualitative validation. The displacement controls as the loading condition were applied effectively to simulate occlusal behaviors in 2 cases of teeth movement of molar teeth.

Keywords: cranium, finite element analysis, mandible, masticatory action, occlusal force

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Authors: Beth Taylor, Kojima Mituaki, Atsushi Senda, Koji Morishita, Yasuhiro Otomo

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Intestinal ischaemia-reperfusion injury drives systemic inflammation and organ failure following trauma/haemorrhagic shock (T/HS), through the release of pro-inflammatory mediators into the mesenteric lymph (ML). However, changes in the biological function of ML are not fully understood, and therefore, a specific model of intestinal ischaemia-reperfusion injury is required to obtain ML for the study of its biological function upon inflammatory cells. ML obtained from a model of intestinal ischaemia-reperfusion injury was used to assess biological function upon inflammatory cells and investigate changes in the biological function of individual ML components. An additional model was used to determine the effect of vagal nerve stimulation (VNS) upon biological function. Rat ML was obtained by mesenteric lymphatic duct cannulation before and after occlusion of the superior mesenteric artery (SMAO). ML was incubated with human polymorphonuclear neutrophils (PMNs), monocytes and lymphocytes, and the biological function of these cells was assessed. ML was then separated into supernatant, exosome and micro-vesicle components, and biological activity was compared in monocytes. A model with an additional VNS phase was developed, in which the right cervical vagal nerve was exposed and stimulated, and ML collected for comparison of biological function with the conventional model. The biological function of ML was altered by intestinal ischaemia-reperfusion injury, increasing PMN activation, monocyte activation, and lymphocyte apoptosis. Increased monocyte activation was only induced by the exosome component of ML, with no significant changes induced by the supernatant or micro-vesicle components. VNS partially attenuated monocyte activation, but no attenuation of PMN activation was observed. Intestinal ischaemia-reperfusion injury induces changes in the biological function of ML upon both innate and adaptive inflammatory cells, supporting the role of intestinal ischaemia-reperfusion injury in driving systemic inflammation following T/HS. The exosome component of ML appears to be critical to the transport of pro-inflammatory mediators in ML. VNS partially attenuates changes in innate inflammatory cell biological activity observed, presenting possibilities for future novel treatment development in multiple organ failure patients.

Keywords: exosomes, inflammation, intestinal ischaemia, mesenteric lymph, vagal stimulation

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Authors: Suchithra V., Shreedhanya, Kavya Menon, Vidya Niranjan

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Skin metagenomics has a wide range of applications with direct relevance to the health of the organism. It gives us insight to the diverse community of microorganisms (the microbiome) harbored on the skin. In the recent years, it has become increasingly apparent that the interaction between skin microbiome and the human body plays a prominent role in immune system development, cancer development, disease pathology, and many other biological implications. Next Generation Sequencing has led to faster and better understanding of environmental organisms and their mutual interactions. This project is studying the human skin microbiome of different individuals having varied skin conditions. Bacterial 16S rRNA data of skin microbiome is downloaded from SRA toolkit provided by NCBI to perform metagenomics analysis. Twelve samples are selected with two controls, and 3 different categories, i.e., sex (male/female), skin type (moist/intermittently moist/sebaceous) and occlusion (occluded/intermittently occluded/exposed). Quality of the data is increased using Cutadapt, and its analysis is done using FastQC. USearch, a tool used to analyze an NGS data, provides a suitable platform to obtain taxonomy classification and abundance of bacteria from the metagenome data. The statistical tool used for analyzing the USearch result is METAGENassist. The results revealed that the top three abundant organisms found were: Prevotella, Corynebacterium, and Anaerococcus. Prevotella is known to be an infectious bacterium found on wound, tooth cavity, etc. Corynebacterium and Anaerococcus are opportunist bacteria responsible for skin odor. This result infers that Prevotella thrives easily in sebaceous skin conditions. Therefore it is better to undergo intermittently occluded treatment such as applying ointments, creams, etc. to treat wound for sebaceous skin type. Exposing the wound should be avoided as it leads to an increase in Prevotella abundance. Moist skin type individuals can opt for occluded or intermittently occluded treatment as they have shown to decrease the abundance of bacteria during treatment.

Keywords: bacterial 16S rRNA , next generation sequencing, skin metagenomics, skin microbiome, taxonomy

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Authors: Ecem Deniz Kırkpantur, Ozge Ecmel Onur, Tuba Cimilli Ozturk, Ebru Unal Akoglu

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Moyamoya disease is a unique chronic progressive cerebrovascular disease characterized by bilateral stenosis or occlusion of the arteries around the circle of Willis with prominent arterial collateral circulation. The occurrence of Moyamoya disease is related to immune, genetic and other factors. There is no curative treatment for Moyamoya disease. Secondary prevention for patients with symptomatic Moyamoya disease is largely centered on surgical revascularization techniques. We present here a 62-year old male presented with headache and vision loss for 2 days. He was previously diagnosed with hypertension and glaucoma. On physical examination, left eye movements were restricted medially, both eyes were hyperemic and their movements were painful. Other neurological and physical examination were normal. His vital signs and laboratory results were within normal limits. Computed tomography (CT) showed dilated vascular structures around both lateral ventricles and atherosclerotic changes inside the walls of internal carotid artery (ICA). Magnetic resonance imaging (MRI) and angiography (MRA) revealed dilated venous vascular structures around lateral ventricles and hyper-intense gliosis in periventricular white matter. Ischemic gliosis around the lateral ventricles were present in the Digital Subtracted Angiography (DSA). After the neurology, ophthalmology and neurosurgery consultation, the patient was diagnosed with Moyamoya disease, pulse steroid therapy was started for vision loss, and super-selective DSA was planned for further investigation. Moyamoya disease is a rare condition, but it can be an important cause of stroke in both children and adults. It generally affects anterior circulation, but posterior cerebral circulation may also be affected, as well. In the differential diagnosis of acute vision loss, occipital stroke related to Moyamoya disease should be considered. Direct and indirect surgical revascularization surgeries may be used to effectively revascularize affected brain areas, and have been shown to reduce risk of stroke.

Keywords: headache, Moyamoya disease, stroke, visual loss

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Authors: Adkham Paiziev, Fikrat Kerimov

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Near Infrared Spectroscopy (NIRS) is one of the biophotonic techniques which can be used to monitor oxygenation and hemodynamics in a variety of human tissues, including skeletal muscle. In the present work, we are offering tissue oximetry (OxyPrem) to measure hemodynamic parameters of skeletal muscles in rest and exercise. Purpose: - To elaborate the new wireless, portable, noninvasive, wearable NIRS device to measure skeletal muscle oxygenation during exercise. - To test this device on brachioradialis muscle of wrestler volunteers by using combined method of arterial occlusion (AO) and NIRS (AO+NIRS). Methods: Oxyprem NIRS device has been used together with AO test. AO test and Isometric brachioradialis muscle contraction experiments have been performed on one group of wrestler volunteers. ‘Accu- Measure’ caliper (USA) to measure skinfold thickness (SFT) has been used. Results: Elaborated device consists on power supply box, a sensor head and installed ‘Tubis’ software for data acquisition and to compute deoxyhemoglobin ([HHb), oxyhemoglobin ([O2Hb]), tissue oxygenation (StO2) and muscle tissue oxygen consumption (mVO2). Sensor head consists on four light sources with three light emitting diodes with nominal wavelengths of 760 nm, 805 nm, and 870 nm, and two detectors. AO and isometric voluntary forearm muscle contraction (IVFMC) on five healthy male subjects (23,2±0.84 in age, 0.43±0.05cm of SFT ) and four female subjects (22.0±1.0 in age and 0.24±0.04 cm SFT) has been measured. mVO2 for control group has been calculated (-0.65%/sec±0.07) for male and -0.69%/±0.19 for female subjects). Tissue oxygenation index for wrestlers in average about 75% whereas for control group StO2 =63%. Second experiment was connected with quality monitoring muscle activity during IVFMC at 10%,30% and 50% of MVC. It has been shown, that the concentration changes of HbO2 and HHb positively correlated to the contraction intensity. Conclusion: We have presented a portable multi-channel wireless NIRS device for real-time monitoring of muscle activity. The miniaturized NIRS sensor and the usage of wireless communication make the whole device have a compact-size, thus can be used in muscle monitoring.

Keywords: skeletal muscle, oxygenation, instrumentation, near infrared spectroscopy

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Authors: Showkat Ahmad Bhat, Iqra Reyaz, Falaque ul Afshan, Ahmad Arif Reshi, Muneeb U. Rehman, Manzoor R. Mir, Sabhiya Majid, Sonallah, Sheikh Bilal, Ishraq Hussain

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Background: Gastric cancer is the fourth most common cancer and the second leading cause of worldwide cancer-related deaths, with a wide variation in incidence rates across different geographical areas. The current view of cancer is that a malignancy arises from a transformation of the genetic material of a normal cell, followed by successive mutations and by chain of alterations in genes such as DNA repair genes, oncogenes, Tumor suppressor genes. Minerals are necessary for the functioning of several transcriptional factors, proteins that recognize certain DNA sequences and have been found to play a role in gastric cancer. Material Methods:The present work was a case control study and its aim was to ascertain the role of minerals and promoter hypermethylation of CpG islands of DAP-K gene in Gastric cancer patients among the Kashmiri population. Serum was extracted from all the samples and mineral estimation was done by AAS from serum, DNA was also extracted and was modified using bisulphite modification kit. Methylation-specific PCR was used for the analysis of the promoter hypermethylation status of DAP-K gene. The epigenetic analysis revealed that unlike other high risk regions, Kashmiri population has a different promoter hypermethylation profile of DAP-K gene and has different mineral profile. Results: In our study mean serum copper levels were significantly different for the two genders (p<0.05), while as no significant differences were observed for iron and zinc levels. In Methylation-specific PCR the methylation status of the promoter region of DAP-K gene was as 67.50% (27/40) of the gastric cancer tissues showed methylated DAP-K promoter and 32.50% (13/40) of the cases however showed unmethylated DAP-K promoter. Almost all 85% (17/20) of the histopathologically confirmed normal tissues showed unmethylated DAP-K promoter except only in 3 cases where DAP-K promoter was found to be methylated. The association of promoter hypermethylation with gastric cancer was evaluated by χ2 (Chi square) test and was found to be significant (P=0.0006). Occurrence of DAP-K methylation was found to be unequally distributed in males and females with more frequency in males than in females but the difference was not statistically significant (P =0.7635, Odds ratio=1.368 and 95% C.I=0.4197 to 4.456). When the frequency of DAP-K promoter methylation was compared with clinical staging of the disease, DAP-K promoter methylation was found to be certainly higher in Stage III/IV (85.71%) compared to Stage I/ II (57.69%) but the difference was not statistically significant (P =0.0673). These results suggest that DAP-K aberrant promoter hypermethylation in Kashmiri population contributes to the process of carcinogenesis in Gastric cancer and is reportedly one of the commonest epigenetic changes in the development of Gastric cancer.

Keywords: gastric cancer, minerals, AAS, hypermethylation, CpG islands, DAP-K gene

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Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

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Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

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Authors: Dor Oppenheim, Yael Edan, Guy Shani

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This paper presents an image analysis algorithm to detect and count yellow tomato flowers in a greenhouse with uneven illumination conditions, complex growth conditions and different flower sizes. The algorithm is designed to be employed on a drone that flies in greenhouses to accomplish several tasks such as pollination and yield estimation. Detecting the flowers can provide useful information for the farmer, such as the number of flowers in a row, and the number of flowers that were pollinated since the last visit to the row. The developed algorithm is designed to handle the real world difficulties in a greenhouse which include varying lighting conditions, shadowing, and occlusion, while considering the computational limitations of the simple processor in the drone. The algorithm identifies flowers using an adaptive global threshold, segmentation over the HSV color space, and morphological cues. The adaptive threshold divides the images into darker and lighter images. Then, segmentation on the hue, saturation and volume is performed accordingly, and classification is done according to size and location of the flowers. 1069 images of greenhouse tomato flowers were acquired in a commercial greenhouse in Israel, using two different RGB Cameras – an LG G4 smartphone and a Canon PowerShot A590. The images were acquired from multiple angles and distances and were sampled manually at various periods along the day to obtain varying lighting conditions. Ground truth was created by manually tagging approximately 25,000 individual flowers in the images. Sensitivity analyses on the acquisition angle of the images, periods throughout the day, different cameras and thresholding types were performed. Precision, recall and their derived F1 score were calculated. Results indicate better performance for the view angle facing the flowers than any other angle. Acquiring images in the afternoon resulted with the best precision and recall results. Applying a global adaptive threshold improved the median F1 score by 3%. Results showed no difference between the two cameras used. Using hue values of 0.12-0.18 in the segmentation process provided the best results in precision and recall, and the best F1 score. The precision and recall average for all the images when using these values was 74% and 75% respectively with an F1 score of 0.73. Further analysis showed a 5% increase in precision and recall when analyzing images acquired in the afternoon and from the front viewpoint.

Keywords: agricultural engineering, image processing, computer vision, flower detection

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Authors: Chi-Feng Lai, Wen-Chun Liao Liao

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Many people are bothered by sleep difficulties in Taiwan’s society. However, majority of patients get medical treatments without a comprehensive sleep assessment. It is still a big challenge to formulate a comprehensive assessment of sleep difficulties in clinical settings, even though many assessment tools have existed in literature. This study tries to implement reliable and effective ‘comprehensive sleep assessment scales’ in a medical center and to explore differences in sleep-related factors between clinic clients with or without sleep difficulty complaints. The comprehensive sleep assessment (CSA) scales were composed of 5 dimensions: ‘personal factors’, ‘physiological factors’, ‘psychological factors’, ‘social factors’ and ‘environmental factors, and were first evaluated by expert validity and 20 participants with test-retest reliability. The Content Validity Index (CVI) of the CSA was 0.94 and the alpha of the consistency reliability ranged 0.996-1.000. Clients who visited sleep clinic due to sleep difficulties (n=32, 16 males and 16 females, ages 43.66 ±14.214) and gender-and age- matched healthy subjects without sleep difficulties (n=96, 47 males and 49 females, ages 41.99 ±13.69) were randomly recruited at a ratio of 1:3 (with sleep difficulties vs. without sleep difficulties) to compare their sleep and the CSA factors. Results show that all clinic clients with sleep difficulties did have poor sleep quality (PSQI>5) and mild to moderate daytime sleepiness (ESS >11). Personal factors of long working hours (χ2= 10.315, p=0.001), shift workers (χ2= 8.964, p=0.003), night shift (χ2=9.395, p=0.004) and perceived stress (χ2=9.503, p=0.002) were disruptors of sleep difficulties. Physiological factors from physical examination including breathing by mouth, low soft palate, high narrow palate, Edward Angle, tongue hypertrophy, and occlusion of the worn surface were observed in clinic clients. Psychological factors including higher perceived stress (χ2=32.542, p=0.000), anxiety and depression (χ2=32.868, p=0.000); social factors including lack of leisure activities (χ2=39.857, p=0.000), more drinking habits (χ2=1.798, p=0.018), irregular amount and frequency in meals (χ2=5.086, p=0.024), excessive dinner (χ2=21.511, p=0.000), being incapable of getting up on time due to previous poor night sleep (χ2=4.444, p=0.035); and environmental factors including lights (χ2=7.683, p=0.006), noise (χ2=5.086, p=0.024), low or high bedroom temperature (χ2=4.595, p=0.032) were existed in clients. In conclusion, the CSA scales can work as valid and reliable instruments for evaluating sleep-related factors. Findings of this study provide important reference for assessing clinic clients with sleep difficulties.

Keywords: comprehensive sleep assessment, sleep-related factors, sleep difficulties

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Authors: Aya Al Masri, Stefaan Carpentier, Fabrice Leroy, Thibault Julien, Safoin Aktaou, Malorie Martin, Fouad Maaloul

Abstract:

Introduction: During an 'Interventional Radiology (IR)' procedure, the patient's skin-dose may become very high for a burn, necrosis and ulceration to appear. In order to prevent these deterministic effects, an accurate calculation of the patient skin-dose mapping is essential. For most machines, the 'Dose Area Product (DAP)' and fluoroscopy time are the only information available for the operator. These two parameters are a very poor indicator of the peak skin dose. We developed a mathematical model that reconstructs the magnitude (delivered dose), shape, and localization of each irradiation field on the patient skin. In case of critical dose exceeding, the system generates warning alerts. We present the results of its comparison with clinical studies. Materials and methods: Two series of comparison of the skin-dose mapping of our mathematical model with clinical studies were performed: 1. At a first time, clinical tests were performed on patient phantoms. Gafchromic films were placed on the table of the IR machine under of PMMA plates (thickness = 20 cm) that simulate the patient. After irradiation, the film darkening is proportional to the radiation dose received by the patient's back and reflects the shape of the X-ray field. After film scanning and analysis, the exact dose value can be obtained at each point of the mapping. Four experimentation were performed, constituting a total of 34 acquisition incidences including all possible exposure configurations. 2. At a second time, clinical trials were launched on real patients during real 'Chronic Total Occlusion (CTO)' procedures for a total of 80 cases. Gafchromic films were placed at the back of patients. We performed comparisons on the dose values, as well as the distribution, and the shape of irradiation fields between the skin dose mapping of our mathematical model and Gafchromic films. Results: The comparison between the dose values shows a difference less than 15%. Moreover, our model shows a very good geometric accuracy: all fields have the same shape, size and location (uncertainty < 5%). Conclusion: This study shows that our model is a reliable tool to warn physicians when a high radiation dose is reached. Thus, deterministic effects can be avoided.

Keywords: clinical experimentation, interventional radiology, mathematical model, patient's skin-dose mapping.

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Authors: Humaira M. Khan, Kanwal Asif

Abstract:

Ischemic stroke is a neurological disorder with a complex pathophysiology associated with motor, sensory and cognitive deficits. Major approaches developed to treat acute ischemic stroke fall into two categories, thrombolysis and neuroprotection. The objectives of this study were to evaluate the neuroprotective and anti-thrombolytic effects of Olea europaea (olive oil) and Malus domestica (apple cider vinegar) and their combination in rat stroke model. Furthermore, histopathological analysis was also performed to assess the severity of ischemia among treated and reference groups. Male albino rats (12 months age) weighing 300- 350gm were acclimatized and subjected to middle cerebral artery occlusion method for stroke induction. Olea europaea and Malus domestica was administered orally in dose of 0.75ml/kg and 3ml/kg and combination was administered at dose of 0.375ml/kg and 1.5ml/kg prophylactically for consecutive 21 days. Negative control group was dosed with normal saline whereas piracetam (250mg/kg) was administered as reference. Neuroprotective activity of standard piracetam, Olea europaea, Malus domestica and their combination was evaluated by performing functional outcome tests i.e. Cylinder, pasta, ladder run, pole and water maize tests. Rats were subjected to surgery after 21 days of treatment for analysis from stroke recovery. Olea europaea and Malus domestica in individual doses of 0.75ml/kg and 3ml/kg respectively showed neuroprotection by significant improvement in ladder run test (121.6± 0.92;128.2 ± 0.73) as compare to reference (125.4 ± 0.74). Both test doses showed significant neuroprotection as compare to reference (9.60 ± 0.50) in pasta test (8.40 ± 0.24;9.80 ± 0.37) whereas with cylinder test, experimental groups showed significant increase in movements (6.60 ± 0.24; 8.40 ± 0.24) in contrast to reference (7.80 ± 0.37).There was a decrease in percentage time taken f to reach the hidden maize in water maize test (56.80 ± 0.58;61.80 ± 0.66) at doses 0.75ml/kg and 3ml/kg respectively as compare to piracetam (59.40 ± 1.07). Olea europaea and Malus domestica individually showed significant reduction in duration of mobility (127.0 ± 0.44; 123.0 ± 0.44) in pole test as compare to piracetam (124.0 ± 0.70). Histopathological analysis revealed the significant extent of protection from ischemia after prophylactic treatments. Hence it is concluded that Olea europaea and Malus domestica are effective neuroprotective agents alone as compare to their combination.

Keywords: ischemia, Malus domestica, neuroprotection, Olea europaea

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