Search results for: diabetes diagnosis
Commenced in January 2007
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Edition: International
Paper Count: 2821

Search results for: diabetes diagnosis

1681 Neural Network and Support Vector Machine for Prediction of Foot Disorders Based on Foot Analysis

Authors: Monireh Ahmadi Bani, Adel Khorramrouz, Lalenoor Morvarid, Bagheri Mahtab

Abstract:

Background:- Foot disorders are common in musculoskeletal problems. Plantar pressure distribution measurement is one the most important part of foot disorders diagnosis for quantitative analysis. However, the association of plantar pressure and foot disorders is not clear. With the growth of dataset and machine learning methods, the relationship between foot disorders and plantar pressures can be detected. Significance of the study:- The purpose of this study was to predict the probability of common foot disorders based on peak plantar pressure distribution and center of pressure during walking. Methodologies:- 2323 participants were assessed in a foot therapy clinic between 2015 and 2021. Foot disorders were diagnosed by an experienced physician and then they were asked to walk on a force plate scanner. After the data preprocessing, due to the difference in walking time and foot size, we normalized the samples based on time and foot size. Some of force plate variables were selected as input to a deep neural network (DNN), and the probability of any each foot disorder was measured. In next step, we used support vector machine (SVM) and run dataset for each foot disorder (classification of yes or no). We compared DNN and SVM for foot disorders prediction based on plantar pressure distributions and center of pressure. Findings:- The results demonstrated that the accuracy of deep learning architecture is sufficient for most clinical and research applications in the study population. In addition, the SVM approach has more accuracy for predictions, enabling applications for foot disorders diagnosis. The detection accuracy was 71% by the deep learning algorithm and 78% by the SVM algorithm. Moreover, when we worked with peak plantar pressure distribution, it was more accurate than center of pressure dataset. Conclusion:- Both algorithms- deep learning and SVM will help therapist and patients to improve the data pool and enhance foot disorders prediction with less expense and error after removing some restrictions properly.

Keywords: deep neural network, foot disorder, plantar pressure, support vector machine

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1680 The Enzyme Inhibitory Potentials of Different Extracts from Linaria genistifolia subsp. genistifolia

Authors: Gokhan Zengin, Abdurrahman Aktumsek

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The key enzyme inhibitory theory is one of the most accepted strategies in the treatment of global health problems including Alzheimer’s Disease and Diabetes mellitus. For this reason, the enzyme inhibitory potentials of different solvent extracts from Linaria genistifolia subsp. genistifolia were investigated against cholinesterase, and tyrosinase. The in vitro enzyme inhibitory potentials were measured with a microplate reader. The acetone and methanol extracts exhibited the strongest enzyme inhibitory effects on cholinesterase. However, the water extract was only active on tyrosinase. The results suggested that Linaria genistifolia subsp. genistifolia could be considered as a source of natural enzyme inhibitors for the treatment of major health problems.

Keywords: enzyme inhibitors, cholinesterase, tyrosinase, linaria, Turkey

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1679 Impacts and Implications: Exploring the Long-Term Health Benefits of Regular Physical Activity

Authors: Muhammad Wahb

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Physical activity is increasingly recognized as a significant factor in maintaining optimal health and preventing chronic diseases. This research scrutinizes the long-term health benefits of sustained physical activity, employing a systematic review of epidemiological studies and randomized control trials conducted over the past decade. The study illuminates the protective effects of regular physical activity against cardiovascular disease, obesity, diabetes, and mental health disorders, with a special focus on the mechanisms involved. Furthermore, the paper provides insights into how public health initiatives can effectively promote physical activity among diverse populations, contributing to improved community health outcomes.

Keywords: physical activity, long-term health benefits, chronic disease prevention, public health

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1678 Pathologies in the Left Atrium Reproduced Using a Low-Order Synergistic Numerical Model of the Cardiovascular System

Authors: Nicholas Pearce, Eun-jin Kim

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Pathologies of the cardiovascular (CV) system remain a serious and deadly health problem for human society. Computational modelling provides a relatively accessible tool for diagnosis, treatment, and research into CV disorders. However, numerical models of the CV system have largely focused on the function of the ventricles, frequently overlooking the behaviour of the atria. Furthermore, in the study of the pressure-volume relationship of the heart, which is a key diagnosis of cardiac vascular pathologies, previous works often evoke popular yet questionable time-varying elastance (TVE) method that imposes the pressure-volume relationship instead of calculating it consistently. Despite the convenience of the TVE method, there have been various indications of its limitations and the need for checking its validity in different scenarios. A model of the combined left ventricle (LV) and left atrium (LA) is presented, which consistently considers various feedback mechanisms in the heart without having to use the TVE method. Specifically, a synergistic model of the left ventricle is extended and modified to include the function of the LA. The synergy of the original model is preserved by modelling the electro-mechanical and chemical functions of the micro-scale myofiber for the LA and integrating it with the microscale and macro-organ-scale heart dynamics of the left ventricle and CV circulation. The atrioventricular node function is included and forms the conduction pathway for electrical signals between the atria and ventricle. The model reproduces the essential features of LA behaviour, such as the two-phase pressure-volume relationship and the classic figure of eight pressure-volume loops. Using this model, disorders in the internal cardiac electrical signalling are investigated by recreating the mechano-electric feedback (MEF), which is impossible where the time-varying elastance method is used. The effects of AV node block and slow conduction are then investigated in the presence of an atrial arrhythmia. It is found that electrical disorders and arrhythmia in the LA degrade the CV system by reducing the cardiac output, power, and heart rate.

Keywords: cardiovascular system, left atrium, numerical model, MEF

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1677 A Preliminary in vitro Investigation of the Acetylcholinesterase and α-Amylase Inhibition Potential of Pomegranate Peel Extracts

Authors: Zoi Konsoula

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The increasing prevalence of Alzheimer’s disease (AD) and diabetes mellitus (DM) constitutes them major global health problems. Recently, the inhibition of key enzyme activity is considered a potential treatment of both diseases. Specifically, inhibition of acetylcholinesterase (AChE), the key enzyme involved in the breakdown of the neurotransmitter acetylcholine, is a promising approach for the treatment of AD, while inhibition of α-amylase retards the hydrolysis of carbohydrates and, thus, reduces hyperglycemia. Unfortunately, commercially available AChE and α-amylase inhibitors are reported to possess side effects. Consequently, there is a need to develop safe and effective treatments for both diseases. In the present study, pomegranate peel (PP) was extracted using various solvents of increasing polarity, while two extraction methods were employed, the conventional maceration and the ultrasound assisted extraction (UAE). The concentration of bioactive phytoconstituents, such as total phenolics (TPC) and total flavonoids (TFC) in the prepared extracts was evaluated by the Folin-Ciocalteu and the aluminum-flavonoid complex method, respectively. Furthermore, the anti-neurodegenerative and anti-hyperglycemic activity of all extracts was determined using AChE and α-amylase inhibitory activity assays, respectively. The inhibitory activity of the extracts against AChE and α-amylase was characterized by estimating their IC₅₀ value using a dose-response curve, while galanthamine and acarbose were used as positive controls, respectively. Finally, the kinetics of AChE and α-amylase in the presence of the most inhibitory potent extracts was determined by the Lineweaver-Burk plot. The methanolic extract prepared using the UAE contained the highest amount of phytoconstituents, followed by the respective ethanolic extract. All extracts inhibited acetylcholinesterase in a dose-dependent manner, while the increased anticholinesterase activity of the methanolic (IC₅₀ = 32 μg/mL) and ethanolic (IC₅₀ = 42 μg/mL) extract was positively correlated with their TPC content. Furthermore, the activity of the aforementioned extracts was comparable to galanthamine. Similar results were obtained in the case of α-amylase, however, all extracts showed lower inhibitory effect on the carbohydrate hydrolyzing enzyme than on AChE, since the IC₅₀ value ranged from 84 to 100 μg/mL. Also, the α-amylase inhibitory effect of the extracts was lower than acarbose. Finally, the methanolic and ethanolic extracts prepared by UAE inhibited both enzymes in a mixed (competitive/noncompetitive) manner since the Kₘ value of both enzymes increased in the presence of extracts, while the Vmax value decreased. The results of the present study indicate that PP may be a useful source of active compounds for the management of AD and DM. Moreover, taking into consideration that PP is an agro-industrial waste product, its valorization could not only result in economic efficiency but also reduce the environmental pollution.

Keywords: acetylcholinesterase, Alzheimer’s disease, α-amylase, diabetes mellitus, pomegranate

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1676 Joubert Syndrome and Related Disorders: A Single Center Experience

Authors: Ali Al Orf, Khawaja Bilal Waheed

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Background and objective: Joubert syndrome (JS) is a rare, autosomal-recessive condition. Early recognition is important for management and counseling. Magnetic resonance imaging (MRI) can help in diagnosis. Therefore, we sought to evaluate clinical presentation and MRI findings in Joubert syndrome and related disorders. Method: A retrospective review of genetically proven cases of Joubert syndromes and related disorders was reviewed for their clinical presentation, demographic information, and magnetic resonance imaging findings in a period of the last 10 years. Two radiologists documented magnetic resonance imaging (MRI) findings. The presence of hypoplasia of the cerebellar vermis with hypoplasia of the superior cerebellar peduncle resembling the “Molar Tooth Sign” in the mid-brain was documented. Genetic testing results were collected to label genes linked to the diagnoses. Results: Out of 12 genetically proven JS cases, most were females (9/12), and nearly all presented with hypotonia, ataxia, developmental delay, intellectual impairment, and speech disorders. 5/12 children presented at age of 1 or below. The molar tooth sign was seen in 10/12 cases. Two cases were associated with other brain findings. Most of the cases were found associated with consanguineous marriage Conclusion and discussion: The molar tooth sign is a frequent and reliable sign of JS and related disorders. Genes related to defective cilia result in malfunctioning in the retina, renal tubule, and neural cell migration, thus producing heterogeneous syndrome complexes known as “ciliopathies.” Other ciliopathies like Senior-Loken syndrome, Bardet Biedl syndrome, and isolated nephronophthisis must be considered as the differential diagnosis of JS. The main imaging findings are the partial or complete absence of the cerebellar vermis, hypoplastic cerebellar peduncles (giving MTS), and (bat-wing appearance) fourth ventricular deformity. LimitationsSingle-center, small sample size, and retrospective nature of the study were a few of the study limitations.

Keywords: Joubart syndrome, magnetic resonance imaging, molar tooth sign, hypotonia

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1675 MR Imaging Spectrum of Intracranial Infections: An Experience of 100 Cases in a Tertiary Hospital in Northern India

Authors: Avik Banerjee, Kavita Saggar

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Infections of the nervous system and adjacent structures are often life-threatening conditions. Despite the recent advances in neuroimaging evaluation, the diagnosis of unclear infectious CNS disease remains a challenge. Our aim is to evaluate the typical and atypical neuro-imaging features of the various routinely encountered CNS infected patients so as to form guidelines for their imaging recognition and differentiation from tumoral, vascular and other entities that warrant a different line of therapy.

Keywords: central nervous system (CNS), Cerebro Spinal Fluid (Csf), Creutzfeldt Jakob Disease (CJD), progressive multifocal leukoencephalopathy (PML)

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1674 Evidence Based Dietary Pattern in South Asian Patients: Setting Goals

Authors: Ananya Pappu, Sneha Mishra

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Introduction: The South Asian population experiences unique health challenges that predisposes this demographic to cardiometabolic diseases at lower BMIs. South Asians may therefore benefit from recommendations specific to their cultural needs. Here, we focus on current BMI guidelines for Asians with a discussion of South Asian dietary practices and culturally tailored interventions. By integrating traditional dietary practices with modern nutritional recommendations, this manuscript aims to highlight effective strategies to improving health outcomes among South Asians. Background: The South Asian community, including individuals from India, Pakistan, Bangladesh, and Sri Lanka, experiences high rates of cardiovascular diseases, cancers, diabetes, and strokes. Notably, the prevalence of diabetes and cardiovascular disease among Asians is elevated at BMIs below the WHO's standard overweight threshold. As it stands, a BMI of 25-30 kg/m² is considered overweight in non-Asians, while this cutoff is reduced to 23-27.4 kg/m² in Asians. This discrepancy can be attributed to studies which have shown different associations between BMI and health risks in Asians compared to other populations. Given these significant challenges, optimizing lifestyle management for cardiometabolic risk factors is crucial. Tailored interventions that consider cultural context seem to be the best approach for ensuring the success of both dietary and physical activity interventions in South Asian patients. Adopting a whole food, plant-based diet (WFPD) is one such strategy. The WFPD suggests that half of one meal should consist of non-starchy vegetables. In the South Asian diet, this includes traditional vegetables such as okra, tindora, eggplant, and leafy greens including amaranth, collards, chard, and mustards. A quarter of the meal should include plant-based protein sources like cooked beans, lentils, and paneer, with the remaining quarter comprising healthy grains or starches such as whole wheat breads, millets, tapioca, and barley. Adherence to the WFPD has been shown to improve cardiometabolic risk factors including weight, BMI, total cholesterol, HbA1c, and reduces the risk of developing non-alcoholic fatty liver disease (NAFLD). Another approach to improving dietary habits is timing meals. Many of the major cultures and religions in the Indian subcontinent incorporate religious fasting. Time-restricted eating (TRE), also known as intermittent fasting, is a practice akin to traditional fasting, which involves consuming all daily calories within a specific window. TRE has been shown to improve insulin resistance in prediabetic and diabetic patients. Common regimens include completing all meals within an 8-hour window, consuming a low-calorie diet every other day, and the 5:2 diet, which involves fasting twice weekly. These fasting practices align with the natural circadian rhythm, potentially enhancing metabolic health and reducing obesity and diabetes risks. Conclusion: South Asians develop cardiometabolic disease at lower BMIs; hence, it is important to counsel patients about lifestyle interventions that decrease their risk. Traditional South Asian diets can be made more nutrient-rich by incorporating vegetables, plant proteins like lentils and beans, and substituting refined grains for whole grains. Ultimately, the best diet is one to which a patient can adhere. It is therefore important to find a regimen that aligns with a patient’s cultural and traditional food practices.

Keywords: BMI, diet, obesity, South Asian, time-restricted eating

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1673 Prediction of Coronary Artery Stenosis Severity Based on Machine Learning Algorithms

Authors: Yu-Jia Jian, Emily Chia-Yu Su, Hui-Ling Hsu, Jian-Jhih Chen

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Coronary artery is the major supplier of myocardial blood flow. When fat and cholesterol are deposit in the coronary arterial wall, narrowing and stenosis of the artery occurs, which may lead to myocardial ischemia and eventually infarction. According to the World Health Organization (WHO), estimated 740 million people have died of coronary heart disease in 2015. According to Statistics from Ministry of Health and Welfare in Taiwan, heart disease (except for hypertensive diseases) ranked the second among the top 10 causes of death from 2013 to 2016, and it still shows a growing trend. According to American Heart Association (AHA), the risk factors for coronary heart disease including: age (> 65 years), sex (men to women with 2:1 ratio), obesity, diabetes, hypertension, hyperlipidemia, smoking, family history, lack of exercise and more. We have collected a dataset of 421 patients from a hospital located in northern Taiwan who received coronary computed tomography (CT) angiography. There were 300 males (71.26%) and 121 females (28.74%), with age ranging from 24 to 92 years, and a mean age of 56.3 years. Prior to coronary CT angiography, basic data of the patients, including age, gender, obesity index (BMI), diastolic blood pressure, systolic blood pressure, diabetes, hypertension, hyperlipidemia, smoking, family history of coronary heart disease and exercise habits, were collected and used as input variables. The output variable of the prediction module is the degree of coronary artery stenosis. The output variable of the prediction module is the narrow constriction of the coronary artery. In this study, the dataset was randomly divided into 80% as training set and 20% as test set. Four machine learning algorithms, including logistic regression, stepwise regression, neural network and decision tree, were incorporated to generate prediction results. We used area under curve (AUC) / accuracy (Acc.) to compare the four models, the best model is neural network, followed by stepwise logistic regression, decision tree, and logistic regression, with 0.68 / 79 %, 0.68 / 74%, 0.65 / 78%, and 0.65 / 74%, respectively. Sensitivity of neural network was 27.3%, specificity was 90.8%, stepwise Logistic regression sensitivity was 18.2%, specificity was 92.3%, decision tree sensitivity was 13.6%, specificity was 100%, logistic regression sensitivity was 27.3%, specificity 89.2%. From the result of this study, we hope to improve the accuracy by improving the module parameters or other methods in the future and we hope to solve the problem of low sensitivity by adjusting the imbalanced proportion of positive and negative data.

Keywords: decision support, computed tomography, coronary artery, machine learning

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1672 Oro-Facial Manifestations of Acute Myeloid Leukaemia -A Case Report

Authors: Aamna Tufail, Kajal Kotecha, Iordanis Toursounidis, Ravinder Pabla

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Introduction/Aims: Acute Myeloid Leukaemia (AML) is a part of leukaemic group of hematopoietic disorders with a varying range of presentations, including oro-facial manifestations. Early recognition and management are essential for favourable outcomes. Materials and Methods: We present our experience, clinical presentation, and clinical photographs of a patient with previously undiagnosed AML who presented with oral symptoms to the emergency department of our hospital. An analysis of clinical characteristics, diagnostic investigations, and management modalities was performed. Results/Statistics: A 58-year-old man presented to A&E reporting an 11-day history of right sided facial swelling, acute TMJ symptoms, and oral discomfort. A dentist ruled out acute dental causes one day post onset of symptoms. Initial assessment was anatomically inconsistent and did not reveal a routine oral or maxillofacial etiology. Detailed clinical examination demonstrated fever, generalised pallor, swelling and erythema of right nasolabial region, bilateral masseteric tenderness, intraoral palatal ecchymosis, palatal ulceration, buccal and labial petechiae, cervical lymphadenopathy, and haematoma on dorsum of right hand overlying right 2nd metacarpal joint. Suspecting a systemic medical cause, we requested haematological investigations, which revealed neutropenia, thrombocytopenia, and anaemia. Flow cytometry confirmed CD34 + AML. Oral discomfort was managed symptomatically. The patient was referred to a tertiary care centre for acute haematologic care, where he was treated with IV antibiotics and continuing cycles of chemotherapy. Conclusions/Clinical Relevance: Oro-facial manifestations may be the first clinical sign of AML. Awareness of its features is vital in early diagnosis. In this context, dentists and oral medicine specialists can play an important role in detecting clinical signs of haematological disorders such as AML.

Keywords: acute myeloid leukaemia, oral symptoms, ulceration, diagnosis, management

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1671 Pleomorphic Dermal Sarcoma: A Management Challenge

Authors: Mona Nada, Fahmy Fahmy

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Background: Pleomorphic dermal sarcoma is a rare form of skin cancer affecting cutaneous layer and, in some cases associated with recurrence and metastasis, very commonly to seen in elderly patient affecting the area of head and neck. Pleomorphic dermal sarcoma rises in ultraviolet light exposed areas. The symptoms and severity of this kind of skin cancer varies according to histological factors. The differentiation of Pleomorphic dermal sarcoma needs extensive immunohistochemistry, as the diagnosis depends mainly on exclusion to rule out other malignancy like poorly differentiated squamous cell carcinoma, melanoma, angiosarcoma and leiomyosarcoma. Objective: assessing the management of Pleomorphic dermal sarcoma in our unit and compared to the updated guidelines. Design: Retrospective study Collection of patient data from medical records at countess of Chester plastic surgery unit of the last 5 years, all histologically confirmed Pleomorphic dermal sarcoma (2017-2023). Data were collected confirmed to be Pleomorphic dermal sarcoma were included in the study. The data collected: clinical description of the lesions at first presentation, operation time, multidisciplinary team discussion, plan, referral as well as second operation and investigation done. With comparison of histological examination, immunohistochemistry staining, the excision and rate of recurrence. Results: data collected N19 from (2017-2023) showed the disease predominantly affecting males and the lesion mainly in head and neck, the diagnosis needed extensive immunohistochemistry to differentiate between other malignancy. recurrence present in numbers of the cases which managed after multidisciplinary team discussion either by excision or radiotherapy. Conclusion: Pleomorphic dermal sarcoma is a rare malignancy which needs more understanding and avoid missing as it is aggressive form of skin cancer, there is a chance of metastasis and recurrence which makes it very important to understand the process of development of the cancer and frequent review of the management guidelines.

Keywords: pleomorphic dermal sarcoma, recurrence, radiotherapy, surgical

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1670 A Comparative Study between Digital Mammography, B Mode Ultrasound, Shear-Wave and Strain Elastography to Distinguish Benign and Malignant Breast Masses

Authors: Arjun Prakash, Samanvitha H.

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BACKGROUND: Breast cancer is the commonest malignancy among women globally, with an estimated incidence of 2.3 million new cases as of 2020, representing 11.7% of all malignancies. As per Globocan data 2020, it accounted for 13.5% of all cancers and 10.6% of all cancer deaths in India. Early diagnosis and treatment can improve the overall morbidity and mortality, which necessitates the importance of differentiating benign from malignant breast masses. OBJECTIVE: The objective of the present study was to evaluate and compare the role of Digital Mammography (DM), B mode Ultrasound (USG), Shear Wave Elastography (SWE) and Strain Elastography (SE) in differentiating benign and malignant breast masses (ACR BI-RADS 3 - 5). Histo-Pathological Examination (HPE) was considered the Gold standard. MATERIALS & METHODS: We conducted a cross-sectional study on 53 patients with 64 breast masses over a period of 10 months. All patients underwent DM, USG, SWE and SE. These modalities were individually assessed to know their accuracy in differentiating benign and malignant masses. All Digital Mammograms were done using the Fujifilm AMULET Innovality Digital Mammography system and all Ultrasound examinations were performed on SAMSUNG RS 80 EVO Ultrasound system equipped with 2 to 9 MHz and 3 – 16 MHz linear transducers. All masses were subjected to HPE. Independent t-test and Chi-square or Fisher’s exact test were used to assess continuous and categorical variables, respectively. ROC analysis was done to assess the accuracy of diagnostic tests. RESULTS: Of 64 lesions, 51 (79.68%) were malignant and 13 (20.31%) (p < 0.0001) were benign. SE was the most specific (100%) (p < 0.0001) and USG (98%) (p < 0.0001) was the most sensitive of all the modalities. E max, E mean, E max ratio, E mean ratio and Strain Ratio of the malignant masses significantly differed from those of the benign masses. Maximum SWE value showed the highest sensitivity (88.2%) (p < 0.0001) among the elastography parameters. A combination of USG, SE and SWE had good sensitivity (86%) (p < 0.0001). CONCLUSION: A combination of USG, SE and SWE improves overall diagnostic yield in differentiating benign and malignant breast masses. Early diagnosis and treatment of breast carcinoma will reduce patient mortality and morbidity.

Keywords: digital mammography, breast cancer, ultrasound, elastography

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1669 The Beneficial Effects of Inhibition of Hepatic Adaptor Protein Phosphotyrosine Interacting with PH Domain and Leucine Zipper 2 on Glucose and Cholesterol Homeostasis

Authors: Xi Chen, King-Yip Cheng

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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

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1668 Design of DNA Origami Structures Using LAMP Products as a Combined System for the Detection of Extended Spectrum B-Lactamases

Authors: Kalaumari Mayoral-Peña, Ana I. Montejano-Montelongo, Josué Reyes-Muñoz, Gonzalo A. Ortiz-Mancilla, Mayrin Rodríguez-Cruz, Víctor Hernández-Villalobos, Jesús A. Guzmán-López, Santiago García-Jacobo, Iván Licona-Vázquez, Grisel Fierros-Romero, Rosario Flores-Vallejo

Abstract:

The group B-lactamic antibiotics include some of the most frequently used small drug molecules against bacterial infections. Nevertheless, an alarming decrease in their efficacy has been reported due to the emergence of antibiotic-resistant bacteria. Infections caused by bacteria expressing extended Spectrum B-lactamases (ESBLs) are difficult to treat and account for higher morbidity and mortality rates, delayed recovery, and high economic burden. According to the Global Report on Antimicrobial Resistance Surveillance, it is estimated that mortality due to resistant bacteria will ascend to 10 million cases per year worldwide. These facts highlight the importance of developing low-cost and readily accessible detection methods of drug-resistant ESBLs bacteria to prevent their spread and promote accurate and fast diagnosis. Bacterial detection is commonly done using molecular diagnostic techniques, where PCR stands out for its high performance. However, this technique requires specialized equipment not available everywhere, is time-consuming, and has a high cost. Loop-Mediated Isothermal Amplification (LAMP) is an alternative technique that works at a constant temperature, significantly decreasing the equipment cost. It yields double-stranded DNA of several lengths with repetitions of the target DNA sequence as a product. Although positive and negative results from LAMP can be discriminated by colorimetry, fluorescence, and turbidity, there is still a large room for improvement in the point-of-care implementation. DNA origami is a technique that allows the formation of 3D nanometric structures by folding a large single-stranded DNA (scaffold) into a determined shape with the help of short DNA sequences (staples), which hybridize with the scaffold. This research aimed to generate DNA origami structures using LAMP products as scaffolds to improve the sensitivity to detect ESBLs in point-of-care diagnosis. For this study, the coding sequence of the CTM-X-15 ESBL of E. coli was used to generate the LAMP products. The set of LAMP primers were designed using PrimerExplorerV5. As a result, a target sequence of 200 nucleotides from CTM-X-15 ESBL was obtained. Afterward, eight different DNA origami structures were designed using the target sequence in the SDCadnano and analyzed with CanDo to evaluate the stability of the 3D structures. The designs were constructed minimizing the total number of staples to reduce costs and complexity for point-of-care applications. After analyzing the DNA origami designs, two structures were selected. The first one was a zig-zag flat structure, while the second one was a wall-like shape. Given the sequence repetitions in the scaffold sequence, both were able to be assembled with only 6 different staples each one, ranging between 18 to 80 nucleotides. Simulations of both structures were performed using scaffolds of different sizes yielding stable structures in all the cases. The generation of the LAMP products were tested by colorimetry and electrophoresis. The formation of the DNA structures was analyzed using electrophoresis and colorimetry. The modeling of novel detection methods through bioinformatics tools allows reliable control and prediction of results. To our knowledge, this is the first study that uses LAMP products and DNA-origami in combination to delect ESBL-producing bacterial strains, which represent a promising methodology for diagnosis in the point-of-care.

Keywords: beta-lactamases, antibiotic resistance, DNA origami, isothermal amplification, LAMP technique, molecular diagnosis

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1667 Ultrasound as an Aid to Predict the Onset of Leaking in Dengue Haemorrhagic Fever: Experience of a Dengue Treatment Facility in South Asia

Authors: Hasn Perera, Is Almeida, Hnk Perera, Mzf Mohammed, Ade Silva, H. Wijesinghe, Ajal Fernando

Abstract:

Introduction: Dengue is a major Public Health burden of two clinical entities, Dengue Fever & Dengue Haemorrhagic Fever (DHF). The vast majority of dengue deaths occur in DHF patients, where the diagnosis hinges on the presence of fluid leakage. Limited Ultrasound Scans (USS) of chest and abdomen are used widely at Centre for Clinical Management of Dengue & Dengue Haemorrhagic Fever (CCMDDHF), as the primary method for detecting fluid leaking in DHF. This study analyses the relationship between haematological and USS findings at the onset of leaking and to further determine the usefulness of ultrasound in diagnosing DHF. Methods: A prospective analysis of 80 serologically confirmed dengue patients initially admitted to a General Medical and Paediatric wards who were subsequently transferred to the CCMDDHF from March to September 2017 were analysed. In addition to repeated blood counts and capillary haematocrits’, serial USS were done to detect the onset fluid leaking by three competent and experienced doctors at CCMDDHF. Results: 80 patients (male: female: 38:42) with a mean age of 20 years (SD ±16.8, range 3-74) were evaluated. Dropping of platelet counts below 100,000 and haematocrit rise towards 20% started 4±1.3 day of fever with a mean platelet value of 69x103(range17-98x103). Gallbladder wall thickening was the commonest (98.7%) USS finding followed by fluid in hepato-renal pouch (95%), pelvic fluid (58.7%), right-sided pleural effusion (35%), bilateral effusions (7.5%). USS evidence of plasma leakage was detected in 11.25 %( n=9) of DHF cases from 1 day before significant haematocrit rise was noted. 35 (43.7%) patients with lowering platelets and haematocrit rise showed no objective evidence of plasma leaking on ultrasound scan. Conclusion: This outbreak underscores the importance of USS as a useful, sensitive and cost-effective tool for early diagnosis of suspected DHF cases, facilitating the tracking of progress of leaking and management of epidemics.

Keywords: dengue, ultrasound, plasma leaking, South Asia

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1666 Unidentified Remains with Extensive Bone Disease without a Clear Diagnosis

Authors: Patricia Shirley Almeida Prado, Selma Paixão Argollo, Maria De Fátima Teixeira Guimarães, Leticia Matos Sobrinho

Abstract:

Skeletal differential diagnosis is essential in forensic anthropology in order to differentiate skeletal trauma from normal osseous variation and pathological processes. Thus, part of forensic anthropological field is differentiate skeletal criminal injuries from the normal skeletal variation (bone fusion or nonunion, transitional vertebrae and other non-metric traits), non-traumatic skeletal pathology (myositis ossificans, arthritis, bone metastasis, osteomyelitis) from traumatic skeletal pathology (myositis ossificans traumatic) avoiding misdiagnosis. This case shows the importance of effective pathological diagnosis in order to accelerate the identification process of skeletonized human remains. THE CASE: An unidentified skeletal remains at the medico legal institute Nina Rodrigues-Salvador, of a male young adult (29 to 40 years estimated) showing a massive heterotopic ossification on its right tibia at upper epiphysis and adjacent articular femur surface; an extensive ossification on the right clavicle (at the sternal extremity) also presenting an heterotopic ossification at right scapulae (upper third of scapulae lateral margin and infraglenoid tubercule) and at the head of right humerus at the shoulder joint area. Curiously, this case also shows an unusual porosity in certain vertebrae´s body and in some tarsal and carpal bones. Likewise, his left fifth metacarpal bones (right and left) showed a healed fracture which led both bones distorted. Based on identification, of pathological conditions in human skeletal remains literature and protocols these alterations can be misdiagnosed and this skeleton may present more than one pathological process. The anthropological forensic lab at Medico-legal Institute Nina Rodrigues in Salvador (Brazil) adopts international protocols to ancestry, sex, age and stature estimations, also implemented well-established conventions to identify pathological disease and skeletal alterations. The most compatible diagnosis for this case is hematogenous osteomyelitis due to following findings: 1: the healed fracture pattern at the clavicle showing a cloaca which is a pathognomonic for osteomyelitis; 2: the metacarpals healed fracture does not present cloaca although they developed a periosteal formation. 3: the superior articular surface of the right tibia shows an extensive inflammatory healing process that extends to adjacent femur articular surface showing some cloaca at tibia bone disease. 4: the uncommon porosities may result from hematogenous infectious process. The fractures probably have occurred in a different moments based on the healing process; the tibia injury is more extensive and has not been reorganized, while metacarpals and clavicle fracture is properly healed. We suggest that the clavicle and tibia´s fractures were infected by an existing infectious disease (syphilis, tuberculosis, brucellosis) or an existing syndrome (Gorham’s disease), which led to the development of osteomyelitis. This hypothesis is supported by the fact that different bones are affected in diverse levels. Like the metacarpals that do not show the cloaca, but then a periosteal new bone formation; then the unusual porosities do not show a classical osteoarthritic processes findings as the marginal osteophyte, pitting and new bone formation, they just show an erosive process without bone formation or osteophyte. To confirm and prove our hypothesis we are working on different clinical approaches like DNA, histopathology and other image exams to find the correct diagnostic.

Keywords: bone disease, forensic anthropology, hematogenous osteomyelitis, human identification, human remains

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1665 Assessment of Cellular Metabolites and Impedance for Early Diagnosis of Oral Cancer among Habitual Smokers

Authors: Ripon Sarkar, Kabita Chaterjee, Ananya Barui

Abstract:

Smoking is one of the leading causes of oral cancer. Cigarette smoke affects various cellular parameters and alters molecular metabolism of cells. Epithelial cells losses their cytoskeleton structure, membrane integrity, cellular polarity that subsequently initiates the process of epithelial cells to mesenchymal transition due to long exposure of cigarette smoking. It changes the normal cellular metabolic activity which induces oxidative stress and enhances the reactive oxygen spices (ROS) formation. Excessive ROS and associated oxidative stress are considered to be a driving force in alteration in cellular phenotypes, polarity distribution and mitochondrial metabolism. Noninvasive assessment of such parameters plays essential role in development of routine screening system for early diagnosis of oral cancer. Electrical cell-substrate impedance sensing (ECIS) is one of such method applied for detection of cellular membrane impedance which can be correlated to cell membrane integrity. Present study intends to explore the alteration in cellular impedance along with the expression of cellular polarity molecules and cytoskeleton distributions in oral epithelial cells of habitual smokers and to correlate the outcome to that of clinically diagnosed oral leukoplakia and oral squamous cell carcinoma patients. Total 80 subjects were categorized into four study groups: nonsmoker (NS), cigarette smoker (CS), oral leukoplakia (OLPK) and oral squamous cell carcinoma (OSCC). Cytoskeleton distribution was analyzed by staining of actin filament and generation of ROS was measured using assay kit using standard protocol. Cell impedance was measured through ECIS method at different frequencies. Expression of E-cadherin and protease-activated receptor (PAR) proteins were observed through immune-fluorescence method. Distribution of actin filament is well organized in NS group however; distribution pattern was grossly varied in CS, OLPK and OSCC. Generation of ROS was low in NS which subsequently increased towards OSCC. Expressions of E-cadherin and change in cellular electrical impedance in different study groups indicated the hallmark of cancer progression from NS to OSCC. Expressions of E-cadherin, PAR protein, and cell impedance were decreased from NS to CS and farther OSCC. Generally, the oral epithelial cells exhibit apico-basal polarity however with cancer progression these cells lose their characteristic polarity distribution. In this study expression of polarity molecule and ECIS observation indicates such altered pattern of polarity among smoker group. Overall the present study monitored the alterations in intracellular ROS generation and cell metabolic function, membrane integrity in oral epithelial cells in cigarette smokers. Present study thus has clinical significance, and it may help in developing a noninvasive technique for early diagnosis of oral cancer amongst susceptible individuals.

Keywords: cigarette smoking, early oral cancer detection, electric cell-substrate impedance sensing, noninvasive screening

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1664 History of Pediatric Renal Pathology

Authors: Mostafa Elbaba

Abstract:

Because childhood renal diseases are grossly different compared to adult diseases, pediatric nephrology was founded as a specialty in 1965. Renal pathology specialty was introduced at the London Ciba Symposium in 1961. The history of renal pathology can be divided into two eras: one starting in the 1650s with the invention of the microscope, the second in the 1950s with the implementation of renal biopsy, and the presence of electron microscopy and immunofluorescence study. Prior to the 1950s, the study of diseased human kidneys was restricted to postmortem examination by gross pathology. In 1827, Richard Bright first described his triad of kidney disease, which was confirmed by morbid kidney changes at autopsy. In 1905 Friedrich Mueller coined the term “nephrosis” describing the inflammatory form of “degenerative” diseases, and later F. Munk added the term “lipoid nephrosis”. The most profound influence on renal diseases’ classification came from the publication of Volhard and Fahr in 1914. In 1899, Carl Max Wilhelm Wilms described Wilms' tumor of the kidneys in children. Chronic pyelonephritis was a popular renal diagnosis and the most common cause of uremia until the 1960s. Although kidney biopsy had been used early in the 1930s for renal tumors, the earliest reports of its use in the diagnosis of medical kidney disease were by Iversen and Brun in 1951, followed by Alwall in 1952, then by Pardo in 1953. The earliest intentional renal biopsies were done in 1944 by Nils Alwall, while the procedure was abandoned after the death of one of his 13 patients who biopsied. In 1950, Antonino Perez-Ara attempted renal biopsies, but his results were missed because of an unpopular journal publication. In the year 1951, Claus Brun and Poul Iverson developed the biopsy procedure using an aspiration technique. Popularizing renal biopsy practice is accredited to Robert Kark, who published his distinct work in 1954. He perfected the technique of renal biopsy in the prone position using the Vim-Silverman needle and used intravenous pyelography to improve the localization of the kidney.

Keywords: history, medicine, nephrology, pediatrics, pathology

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1663 Homeostatic Analysis of the Integrated Insulin and Glucagon Signaling Network: Demonstration of Bistable Response in Catabolic and Anabolic States

Authors: Pramod Somvanshi, Manu Tomar, K. V. Venkatesh

Abstract:

Insulin and glucagon are responsible for homeostasis of key plasma metabolites like glucose, amino acids and fatty acids in the blood plasma. These hormones act antagonistically to each other during the secretion and signaling stages. In the present work, we analyze the effect of macronutrients on the response from integrated insulin and glucagon signaling pathways. The insulin and glucagon pathways are connected by DAG (a calcium signaling component which is part of the glucagon signaling module) which activates PKC and inhibits IRS (insulin signaling component) constituting a crosstalk. AKT (insulin signaling component) inhibits cAMP (glucagon signaling component) through PDE3 forming the other crosstalk between the two signaling pathways. Physiological level of anabolism and catabolism is captured through a metric quantified by the activity levels of AKT and PKA in their phosphorylated states, which represent the insulin and glucagon signaling endpoints, respectively. Under resting and starving conditions, the phosphorylation metric represents homeostasis indicating a balance between the anabolic and catabolic activities in the tissues. The steady state analysis of the integrated network demonstrates the presence of a bistable response in the phosphorylation metric with respect to input plasma glucose levels. This indicates that two steady state conditions (one in the homeostatic zone and other in the anabolic zone) are possible for a given glucose concentration depending on the ON or OFF path. When glucose levels rise above normal, during post-meal conditions, the bistability is observed in the anabolic space denoting the dominance of the glycogenesis in liver. For glucose concentrations lower than the physiological levels, while exercising, metabolic response lies in the catabolic space denoting the prevalence of glycogenolysis in liver. The non-linear positive feedback of AKT on IRS in insulin signaling module of the network is the main cause of the bistable response. The span of bistability in the phosphorylation metric increases as plasma fatty acid and amino acid levels rise and eventually the response turns monostable and catabolic representing diabetic conditions. In the case of high fat or protein diet, fatty acids and amino acids have an inhibitory effect on the insulin signaling pathway by increasing the serine phosphorylation of IRS protein via the activation of PKC and S6K, respectively. Similar analysis was also performed with respect to input amino acid and fatty acid levels. This emergent property of bistability in the integrated network helps us understand why it becomes extremely difficult to treat obesity and diabetes when blood glucose level rises beyond a certain value.

Keywords: bistability, diabetes, feedback and crosstalk, obesity

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1662 Day-Case Ketamine Infusions in Patients with Chronic Pancreatitis

Authors: S. M. C. Kelly, M. Goulden

Abstract:

Introduction: Chronic Pancreatitis is an increasing problem worldwide. Pain is the main symptom and the main reason for hospital readmission following diagnosis, despite the use of strong analgesics including opioids. Ketamine infusions reduce pain in complex regional pain syndrome and other neuropathic pain conditions. Our centre has trialed the use of ketamine infusions in patients with chronic pancreatitis. We have evaluated this service to assess whether ketamine reduces emergency department admissions and analgesia requirements. Methods: This study collected retrospective data from 2010 in all patients who received a ketamine infusion for chronic pain secondary to a diagnosis of chronic pancreatitis. The day-case ketamine infusions were initiated in theatre by an anaesthetist, with standard monitoring and the assistance of an anaesthetic practitioner. A bolus dose of 0.5milligrams/kilogram was given in theatre. The infusion of 0.5 milligrams/kilogram per hour was then administered over a 6 hour period in the theatre recovery area. A study proforma detailed the medical history, analgesic use and admissions to hospital. Patients received a telephone follow up consultation. Results: Over the last eight years, a total of 30 patients have received intravenous ketamine infusions, with a total of 92 ketamine infusions being administered. 53% of the patients were male with the average age of 47. A total of 27 patients participated with the telephone consultation. A third of patients reported a reduction in hospital admissions with pain following the ketamine infusion. Analgesia requirements were reduced by an average of 48.3% (range 0-100%) for an average duration of 69.6 days (range 0-180 days.) Discussion: This service evaluation illustrates that ketamine infusions can reduce analgesic requirements and the number of hospital admissions in patients with chronic pancreatitis. In the light of increasing pressures on Emergency departments and the increasing evidence of the dangers of long-term opioid use, this is clearly a useful finding. We are now performing a prospective study to assess the long-term effectiveness of ketamine infusions in reducing analgesia requirements and improving patient’s quality of life.

Keywords: acute-on-chronic pain, intravenous analgesia infusion, ketamine, pancreatitis

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1661 Impact of 99mTc-MDP Bone SPECT/CT Imaging in Failed Back Surgery Syndrome

Authors: Ching-Yuan Chen, Lung-Kwang Pan

Abstract:

Objective: Back pain is a major health problem costing billions of health budgets annually in Taiwan. Thousands of back pain surgeries are performed annually with up to 40% of patients complaining of back pain at time of post-surgery causing failed back surgery syndrome (FBSS), although diagnosis in these patients may be complex. The aim of study is to assess the feasibility of using bone SPECT-CT imaging to localize the active lesions causing persistent, recurrent or new backache after spine surgery. Materials and Methods: Bone SPECT-CT imaging was performed after the intravenous injection of 20 mCi of 99mTc-MDP for all the patients with diagnosis of FBSS. Patients were evaluated using status of subjectively pain relief, functional improvement and degree of satisfaction by reviewing the medical records and questionnaires in a 2 more years’ follow-up. Results: We enrolled a total of 16 patients were surveyed in our hospital from Jan. 2015 to Dec. 2016. Four people on SPEC/CT imaging ensured significant lesions were undergone a revised surgery (surgical treatment group). The mean visual analogue scale (VAS) decreased 5.3 points and mean Oswestry disability index (ODI) improved 38 points in the surgical group. The remaining 12 on SPECT/CT imaging were diagnosed as no significant lesions then received drug treatment (medical treatment group). The mean VAS only decreased 2 .1 point and mean ODI improved 12.6 points in the medical treatment group. In the posttherapeutic evaluation, the pain of the surgical treatment group showed a satisfactory improvement. In the medical treatment group, 10 of the 12 were also satisfied with the symptom relief while the other 2 did not improve significantly. Conclusions: Findings on SPECT-CT imaging appears to be easily explained the patients' pain. We recommended that SPECT/CT imaging was a feasible and useful clinical tool to improve diagnostic confidence or specificity when evaluating patients with FBSS.

Keywords: failed back surgery syndrome, oswestry disability index, SPECT-CT imaging, 99mTc-MDP, visual analogue scale

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1660 Characterising Rates of Renal Dysfunction and Sarcoidosis in Patients with Elevated Serum Angiotensin-Converting Enzyme

Authors: Fergal Fouhy, Alan O’Keeffe, Sean Costelloe, Michael Clarkson

Abstract:

Background: Sarcoidosis is a systemic, non-infectious disease of unknown aetiology, characterized by non-caseating granulomatous inflammation. The lung is most often affected (90%); however, the condition can affect all organs, including the kidneys. There is limited evidence describing the incidence and characteristics of renal involvement in sarcoidosis. Serum angiotensin-converting enzyme (ACE) is a recognised biomarker used in the diagnosis and monitoring of sarcoidosis. Methods: A single-centre, retrospective cohort study of patients presenting to Cork University Hospital (CUH) in 2015 with first-time elevations of serum ACE was performed. This included an initial database review of ACE and other biochemistry results, followed by a medical chart review to confirm the presence or absence of sarcoidosis and management thereof. Acute kidney injury (AKI) was staged using the AKIN criteria, and chronic kidney disease (CKD) was staged using the KDIGO criteria. Follow-up was assessed over five years tracking serum creatinine, serum calcium, and estimated glomerular filtration rates (eGFR). Results: 119 patients were identified as having a first raised serum ACE in 2015. Seventy-nine male patients and forty female patients were identified. The mean age of patients identified was 47 years old. 11% had CKD at baseline. 18% developed an AKI at least once within the next five years. A further 6% developed CKD during this time period. 13% developed hypercalcemia. The patients within the lowest quartile of serums ACE had an incidence of sarcoidosis of 5%. None of this group developed hypercalcemia, 23% developed AKI, and 7% developed CKD. Of the patients with a serum ACE in the highest quartile, almost all had documented diagnoses of sarcoidosis with an incidence of 96%. 3% of this group developed hypercalcemia, 13% AKI and 3% developed CKD. Conclusions: There was an unexpectedly high incidence of AKI in patients who had a raised serum ACE. Not all patients with a raised serum ACE had a confirmed diagnosis of sarcoidosis. There does not appear to be a relationship between increased serum ACE levels and increased incidence of hypercalcaemia, AKI, and CKD. Ideally, all patients should have biopsy-proven sarcoidosis. This is an initial study that should be replicated with larger numbers and including multiple centres.

Keywords: sarcoidosis, acute kidney injury, chronic kidney disease, hypercalcemia

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1659 Importance of Detecting Malingering Patients in Clinical Setting

Authors: Sakshi Chopra, Harsimarpreet Kaur, Ashima Nehra

Abstract:

Objectives: Malingering is fabricating or exaggerating the symptoms of mental or physical disorders for a variety of secondary gains or motives, which may include financial compensation; avoiding work; getting lighter criminal sentences; or simply to attract attention or sympathy. Malingering is different from somatization disorder and factitious disorder. The prevalence of malingering is unknown and difficult to determine. In an estimated study in forensic population, it can reach up to 17% cases. But the accuracy of such estimates is questionable as successful malingerers are not detected and thus, not included. Methods: The case study of a 58 years old, right handed, graduate, pre-morbidly working in a national company with reported history of stroke leading to head injury; cerebral infarction/facial palsy and dementia. He was referred for disability certification so that his job position can be transferred to his son as he could not work anymore. A series of Neuropsychological tests were administered. Results: With a mental age of < 2.5 years; social adaptive functioning was overall < 20 showing profound Mental Retardation, less than 1 year social age in abilities of self-help, eating, dressing, locomotion, occupation, communication, self-direction, and socialization; severely impaired verbal and performance ability, 96% impairment in Activities of Daily Living, with an indication of very severe depression. With inconsistent and fluctuating medical findings and problem descriptions to different health professionals forming the board for his disability, it was concluded that this patient was malingering. Conclusions: Even though it can be easily defined, malingering can be very challenging to diagnosis. Cases of malingering impose a substantial economic burden on the health care system and false attribution of malingering imposes a substantial burden of suffering on a significant proportion of the patient population. Timely, tactful diagnosis and management can help ease this patient burden on the healthcare system. Malingering can be detected by only trained mental health professionals in the clinical setting.

Keywords: disability, India, malingering, neuropsychological assessment

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1658 Urban Slum Communities Engage in the Fight Against TB in Karnataka, South India

Authors: N. Rambabu, H. Gururaj, Reynold Washington, Oommen George

Abstract:

Motivation: Under the USAID Strengthening Health Outcomes through Private Sector (SHOPS-TB) initiative, Karnataka Health Promotion Trust (KHPT) with technical support of Abt associates is implementing a TB prevention and care model in Karnataka State, South India. KHPT is the interface agency between the public and private sectors, and providers and the target community facilitating early TB case detection and enhancing treatment compliance through private health care providers (pHCP) engagement in RNTCP. The project coverage is 0.84 million urban poor from 663 slums in 12 districts of Karnataka. Problem Statement: India with the highest burden of global TB (26%) and two million cases annually, accounts for approximately one fifth of the global incidence. WHO estimates 300,000 people die from TB annually in India. India expanded the coverage of Directly Observed Treatment, Short-course chemotherapy (DOTS) to the entire country as early as 2006. However, the performance of RNTCP has not been uniform across states. While the national annual new smear-positive (NSP) case notification rate is 53, it is much lower at 47 in Karnataka. A third of TB patients in India reside in urban slums. Approach: Under SHOPS, KHPT actively engages with communities through key opinion leaders and community structures. Interpersonal communication, by Outreach workers through house-to-house visits and at aggregation points, is the primary method used for communication about TB and its management and to increase demand for sputum examination and DOTS. pHCP are mapped, trained and mentored by KHPT. ORWs also provide patient and family counseling on TB treatment, side effects and adherence, screen close contacts of index patients especially children under 6 years of age and screen co-morbidities including HIV, diabetes and malnutrition and risk factors including alcoholism, tobacco use, occupational hazards making appropriate accompanied or documented referrals. A treatment ‘buddy’ system for the patients involving close friends or family members, ICT-based support, DOTS Prerana (inspiration) groups of TB patients, family members and community, DOTS Mitra (friend) helpline services are also used for care and support services. Results: The intervention educated 39988 slum dwellers, referred 1731 chest symptomatics, tested 1061 patients and initiated 248 patients on anti-TB treatment within three months of intervention through continuous community engagement. Conclusions: The intervention’s potential to increase access to preferred health care providers, reduce patient and health system delays in diagnosis and initiation of treatment, improve health seeking behaviour and enhance compliance of pHCPs to standard treatment protocols is being monitored. Initial results are promising.

Keywords: DOTS, KHPT, health outcomes, public and private sector

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1657 The Social Construction of Diagnosis: An Exploratory Study on Gender Dysphoria and Its Implications on Personal Narratives

Authors: Jessica Neri, Elena Faccio

Abstract:

In Europe, except for Denmark and Malta, the legal gender change and the stages of the possible process of gender transition are bound to the diagnosis of a gender identity disorder. The requirement of the evaluation of a mental disorder might have many implications on trans people’s self-representations, interpersonal relations in different social contexts and the therapeutic relations with clinicians during the transition. Psychopathological language may contribute to define the individual’s reality from normative presuppositions with value implications related to the dominant cultural principles. In an effort to mark the boundaries between sanity and pathology, it concurs to the definition of the management procedures of the constructed diversities and deviances, legitimizing the operational practices of particular professional figures. The aim of this research concerns the analysis of the diagnostic category of gender dysphoria contained in the last edition of the Diagnostic and Statistical Manual of Mental Disorders. In particular, this study focuses on the relationship between the implicit and explicit assumptions related to the expressions of gender non-conformity, that sustain the language and the criteria characterizing the Manual, and the possible implications on people’s narratives of transition. In order to achieve this objective two main research methods were used: historical reconstruction of the diagnostic category in the different versions of the Manual and content analysis of that category in the present version. From the historical analysis, in the medical and psychiatric field gender non-conformity has been predominantly explicated by naturalistic perspectives, naming it ‘transsexualism’ and collocating it in the category of gender identity disorder. Currently, pathological judged experiences are represented by gender dysphoria, described in the DSM-5 as the distress that may accompany the incongruence between one's experienced or expressed gender and one's assigned gender, specifying that there must be ‘evidence’ of this. Implicit theories about gender binary, parallelism between gender identity, sex and sexuality and the understanding of the mental health and the subject’s agency as subordinated to the expert knowledge, can be found in the process of designation of the category. A lack of awareness of the historical, social and political aspects connected to the cultural and normative dimensions at the basis of these implicit theories, can be noticed and data given by culture and data given by supposed -biological or psychological- nature, are often confused. This reductionist interpretation of gender and its presumed diversities legitimize the clinician to assume the role of searching and orienting, in a correctional perspective, the biographical elements that correspond to him specific expectations, with no space for other possibilities and identity configurations for people in transition. This research may contribute to the current critical debate about the epistemological foundation of the psychodiagnosis, emphasizing the pragmatic effects on the individuals and on the psychological practice in its wider social context. This work also permits to underline the risks due to the lack of awareness of the processes of social construction of the diagnostic system and its essential role of defence of the values that hold up the symbolic universe of reference.

Keywords: diagnosis, gender dysphoria, narratives, social constructionism

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1656 Assessment, Diagnosis and Treatment, Simulation for the Nurse Practitioner Student

Authors: Helen Coronel, Will Brewer, Peggy Bergeron, Clarissa Hall, Victoria Casson

Abstract:

Simulation-based training provides the nurse practitioner (NP) student with a safe and controlled environment in which they can practice a real-life scenario. This type of learning fosters critical thinking skills essential to practice. The expectation of this study was that students would have an increase in their competency and confidence after performing the simulation. Approximately 8.4% of Americans suffer from depression. The state of Alabama is ranked 47th out of 50 for access to mental health care. As a result of this significant shortage of mental health providers, primary care providers are frequently put in the position of screening for and treating mental health conditions, such as depression. Family nurse practitioners are often utilized as primary care providers, making their ability to assess, diagnose and treat these disorders a necessary skill. The expected outcome of this simulation is an increase in confidence, competency and the empowerment of the nurse practitioner student’s ability to assess, diagnose and treat a common mood disorder they may encounter in practice. The Kirkpatrick Module was applied for this study. A non-experimental design using descriptive statistical analysis was utilized. The simulation was based on a common psychiatric mood disorder frequently observed in primary care and mental health clinics. Students were asked to watch a voiceover power point presentation prior to their on-campus simulation. The presentation included training on the assessment, diagnosis, and treatment of a patient with depression. Prior to the simulation, the students completed a pre-test, then participated in the simulation, and completed a post-test when done. Apple iPads were utilized to access a simulated health record. Major findings of the study support an increase in students’ competency and confidence when assessing, diagnosing, and treating an adult patient with depression.

Keywords: advanced practice, nurse practitioner, simulation, primary care, depression

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1655 A Clinico-Bacteriological Study and Their Risk Factors for Diabetic Foot Ulcer with Multidrug-Resistant Microorganisms in Eastern India

Authors: Pampita Chakraborty, Sukumar Mukherjee

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This study was done to determine the bacteriological profile and antibiotic resistance of the isolates and to find out the potential risk factors for infection with multidrug-resistant organisms. Diabetic foot ulcer is a major medical, social, economic problem and a leading cause of morbidity and mortality, especially in the developing countries like India. 25 percent of all diabetic patients develop a foot ulcer at some point in their lives which is highly susceptible to infections and that spreads rapidly, leading to overwhelming tissue destruction and subsequent amputation. Infection with multidrug resistant organisms (MDRO) may increase the cost of management and may cause additional morbidity and mortality. Proper management of these infections requires appropriate antibiotic selection based on culture and antimicrobial susceptibility testing. Early diagnosis of microbial infections is aimed to institute the appropriate antibacterial therapy initiative to avoid further complications. A total of 200 Type 2 Diabetic Mellitus patients with infection were admitted at GD Hospital and Diabetes Institute, Kolkata. 60 of them who developed ulcer during the year 2013 were included in this study. A detailed clinical history and physical examination were carried out for every subject. Specimens for microbiological studies were obtained from ulcer region. Gram-negative bacilli were tested for extended spectrum Beta-lactamase (ESBL) production by double disc diffusion method. Staphylococcal isolates were tested for susceptibility to oxacillin by screen agar method and disc diffusion. Potential risk factors for MDRO-positive samples were explored. Gram-negative aerobes were most frequently isolated, followed by gram-positive aerobes. Males were predominant in the study and majority of the patients were in the age group of 41-60 years. The presence of neuropathy was observed in 80% cases followed by peripheral vascular disease (73%). Proteus spp. (22) was the most common pathogen isolated, followed by E.coli (17). Staphylococcus aureus was predominant amongst the gram-positive isolates. S.aureus showed a high rate of resistance to antibiotic tested (63.6%). Other gram-positive isolates were found to be highly resistant to erythromycin, tetracycline and ciprofloxacin, 40% each. All isolates were found to be sensitive to Vancomycin and Linezolid. ESBL production was noted in Proteus spp and E.coli. Approximately 70 % of the patients were positive for MDRO. MDRO-infected patients had poor glycemic control (HbA1c 11± 2). Infection with MDROs is common in diabetic foot ulcers and is associated with risk factors like inadequate glycemic control, the presence of neuropathy, osteomyelitis, ulcer size and increased the requirement for surgical treatment. There is a need for continuous surveillance of resistant bacteria to provide the basis for empirical therapy and reduce the risk of complications.

Keywords: diabetic foot ulcer, bacterial infection, multidrug-resistant organism, extended spectrum beta-lactamase

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1654 ADAM10 as a Potential Blood Biomarker of Cognitive Frailty

Authors: Izabela P. Vatanabe, Rafaela Peron, Patricia Manzine, Marcia R. Cominetti

Abstract:

Introduction: Considering the increase in life expectancy of world population, there is an emerging concern in health services to allocate better care and care to elderly, through promotion, prevention and treatment of health. It has been observed that frailty syndrome is prevalent in elderly people worldwide and this complex and heterogeneous clinical syndrome consist of the presence of physical frailty associated with cognitive dysfunction, though in absence of dementia. This can be characterized by exhaustion, unintentional weight loss, decreased walking speed, weakness and low level of physical activity, in addition, each of these symptoms may be a predictor of adverse outcomes such as hospitalization, falls, functional decline, institutionalization, and death. Cognitive frailty is a recent concept in literature, which is defined as the presence of physical frailty associated with mild cognitive impairment (MCI) however in absence of dementia. This new concept has been considered as a subtype of frailty, which along with aging process and its interaction with physical frailty, accelerates functional declines and can result in poor quality of life of the elderly. MCI represents a risk factor for Alzheimer's disease (AD) in view of high conversion rate for this disease. Comorbidities and physical frailty are frequently found in AD patients and are closely related to heterogeneity and clinical manifestations of the disease. The decreased platelets ADAM10 levels in AD patients, compared to cognitively healthy subjects, matched by sex, age and education. Objective: Based on these previous results, this study aims to evaluate whether ADAM10 platelet levels of could act as a biomarker of cognitive frailty. Methods: The study was approved by Ethics Committee of Federal University of São Carlos (UFSCar) and conducted in the municipality of São Carlos, headquarters of Federal University of São Carlos (UFSCar). Biological samples of subjects were collected, analyzed and then stored in a biorepository. ADAM10 platelet levels were analyzed by western blotting technique in subjects with MCI and compared to subjects without cognitive impairment, both with and without presence of frailty. Statistical tests of association, regression and diagnostic accuracy were performed. Results: The results have shown that ADAM10/β-actin ratio is decreased in elderly individuals with cognitive frailty compared to non-frail and cognitively healthy controls. Previous studies performed by this research group, already mentioned above, demonstrated that this reduction is still higher in AD patients. Therefore, the ADAM10/β-actin ratio appears to be a potential biomarker for cognitive frailty. The results bring important contributions to an accurate diagnosis of cognitive frailty from the perspective of ADAM10 as a biomarker for this condition, however, more experiments are being conducted, using a high number of subjects, and will help to understand the role of ADAM10 as biomarker of cognitive frailty and contribute to the implementation of tools that work in the diagnosis of cognitive frailty. Such tools can be used in public policies for the diagnosis of cognitive frailty in the elderly, resulting in a more adequate planning for health teams and better quality of life for the elderly.

Keywords: ADAM10, biomarkers, cognitive frailty, elderly

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1653 Endometrial Biopsy Curettage vs Endometrial Aspiration: Better Modality in Female Genital Tuberculosis

Authors: Rupali Bhatia, Deepthi Nair, Geetika Khanna, Seema Singhal

Abstract:

Introduction: Genital tract tuberculosis is a chronic disease (caused by reactivation of organisms from systemic distribution of Mycobacterium tuberculosis) that often presents with low grade symptoms and non-specific complaints. Patients with genital tuberculosis are usually young women seeking workup and treatment for infertility. Infertility is the commonest presentation due to involvement of the fallopian tubes, endometrium and ovarian damage with poor ovarian volume and reserve. The diagnosis of genital tuberculosis is difficult because of the fact that it is a silent invader of genital tract. Since tissue cannot be obtained from fallopian tubes, the diagnosis is made by isolation of bacilli from endometrial tissue obtained by endometrial biopsy curettage and/or aspiration. Problems are associated with sampling technique as well as diagnostic modality due to lack of adequate sample volumes and the segregation of the sample for various diagnostic tests resulting in non-uniform distribution of microorganisms. Moreover, lack of an efficient sampling technique universally applicable for all specific diagnostic tests contributes to the diagnostic challenges. Endometrial sampling plays a key role in accurate diagnosis of female genital tuberculosis. It may be done by 2 methods viz. endometrial curettage and endometrial aspiration. Both endometrial curettage and aspirate have their own limitations as curettage picks up strip of the endometrium from one of the walls of the uterine cavity including tubal osteal areas whereas aspirate obtains total tissue with exfoliated cells present in the secretory fluid of the endometrial cavity. Further, sparse and uneven distribution of the bacilli remains a major factor contributing to the limitations of the techniques. The sample that is obtained by either technique is subjected to histopathological examination, AFB staining, culture and PCR. Aim: Comparison of the sampling techniques viz. endometrial biopsy curettage and endometrial aspiration using different laboratory methods of histopathology, cytology, microbiology and molecular biology. Method: In a hospital based observational study, 75 Indian females suspected of genital tuberculosis were selected on the basis of inclusion criteria. The women underwent endometrial tissue sampling using Novaks biopsy curette and Karmans cannula. One part of the specimen obtained was sent in formalin solution for histopathological testing and another part was sent in normal saline for acid fast bacilli smear, culture and polymerase chain reaction. The results so obtained were correlated using coefficient of correlation and chi square test. Result: Concordance of results showed moderate agreement between both the sampling techniques. Among HPE, AFB and PCR, maximum sensitivity was observed for PCR, though the specificity was not as high as other techniques. Conclusion: Statistically no significant difference was observed between the results obtained by the two sampling techniques. Therefore, one may use either EA or EB to obtain endometrial samples and avoid multiple sampling as both the techniques are equally efficient in diagnosing genital tuberculosis by HPE, AFB, culture or PCR.

Keywords: acid fast bacilli (AFB), histopatholgy examination (HPE), polymerase chain reaction (PCR), endometrial biopsy curettage

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1652 Silent Myocardial Infarction Presented with Homonymous Hemianopia in a Non-Diabetic Middle Aged Man

Authors: Seyed Fakhroddin Hejazi, Mohammad Saleh Sadeghi, Leili Iranirad

Abstract:

Silent myocardial infarction is defined as the appearance of pathological Q waves in the electrocardiogram, without objective signs of myocardial infarction and any minimal or atypical symptoms. Although this condition has been known for a long time, but little is known about its phenomenon and the mechanisms of it remain unclear. Its coincidence with stroke is also still controversial. This case report introduces a middle-aged man with silent myocardial infarction presented with homonymous hemianopia, which except stage 1 hypertension, had no other major cardiovascular risk factors including diabetes mellitus, hypercholesterolemia, family history of cardiac diseases and smoking. In conclusion, this case report indicated that existence of only one cardiovascular risk factor would lead to the development of MI or stroke.

Keywords: silent myocardial infarction, homonymous hemianopia, stroke, hypertension

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