Search results for: cancer diagnosis and therapy

Authors: Alessandro Poma, Kal Karim, Sergey Piletsky, Giuseppe Battaglia

Abstract:

The recent increasing emergency threat to public health of infectious influenza diseases has prompted interest in the detection of avian influenza virus (AIV) H5N1 in humans as well as animals. A variety of technologies for diagnosing AIV infection have been developed. However, various disadvantages (costs, lengthy analyses, and need for high-containment facilities) make these methods less than ideal in their practical application. Molecularly Imprinted Polymeric Nanoparticles (MIP NPs) are suitable to overcome these limitations by having high affinity, selectivity, versatility, scalability and cost-effectiveness with the versatility of post-modification (labeling – fluorescent, magnetic, optical) opening the way to the potential introduction of improved diagnostic tests capable of providing rapid differential diagnosis. Here we present our first results in the production and testing of MIP NPs for the detection of AIV H5N1. Recent developments in the solid-phase synthesis of MIP NPs mean that for the first time a reliable supply of ‘soluble’ synthetic antibodies can be made available for testing as potential biological or diagnostic active molecules. The MIP NPs have the potential to detect viruses that are widely circulating in farm animals and indeed humans. Early and accurate identification of the infectious agent will expedite appropriate control measures. Thus, diagnosis at an early stage of infection of a herd or flock or individual maximizes the efficiency with which containment, prevention and possibly treatment strategies can be implemented. More importantly, substantiating the practicability’s of these novel reagents should lead to an initial reduction and eventually to a potential total replacement of animals, both large and small, to raise such specific serological materials.

Keywords: influenza virus, molecular imprinting, nanoparticles, polymers

Procedia PDF Downloads 335

Authors: Ravija Gunawardana, Banuka Athuraliya

Abstract:

Machine learning has emerged as a powerful tool for disease diagnosis and prediction. The use of machine learning algorithms has the potential to improve the accuracy of disease prediction, thereby enabling medical professionals to provide more effective and personalized treatments. This study focuses on developing a machine-learning model for disease prediction using symptoms and X-ray images. The importance of this study lies in its potential to assist medical professionals in accurately diagnosing diseases, thereby improving patient outcomes. Respiratory diseases are a significant cause of morbidity and mortality worldwide, and chest X-rays are commonly used in the diagnosis of these diseases. However, accurately interpreting X-ray images requires significant expertise and can be time-consuming, making it difficult to diagnose respiratory diseases in a timely manner. By incorporating machine learning algorithms, we can significantly enhance disease prediction accuracy, ultimately leading to better patient care. The study utilized the Mask R-CNN algorithm, which is a state-of-the-art method for object detection and segmentation in images, to process chest X-ray images. The model was trained and tested on a large dataset of patient information, which included both symptom data and X-ray images. The performance of the model was evaluated using a range of metrics, including accuracy, precision, recall, and F1-score. The results showed that the model achieved an accuracy rate of over 90%, indicating that it was able to accurately detect and segment regions of interest in the X-ray images. In addition to X-ray images, the study also incorporated symptoms as input data for disease prediction. The study used three different classifiers, namely Random Forest, K-Nearest Neighbor and Support Vector Machine, to predict diseases based on symptoms. These classifiers were trained and tested using the same dataset of patient information as the X-ray model. The results showed promising accuracy rates for predicting diseases using symptoms, with the ensemble learning techniques significantly improving the accuracy of disease prediction. The study's findings indicate that the use of machine learning algorithms can significantly enhance disease prediction accuracy, ultimately leading to better patient care. The model developed in this study has the potential to assist medical professionals in diagnosing respiratory diseases more accurately and efficiently. However, it is important to note that the accuracy of the model can be affected by several factors, including the quality of the X-ray images, the size of the dataset used for training, and the complexity of the disease being diagnosed. In conclusion, the study demonstrated the potential of machine learning algorithms for disease prediction using symptoms and X-ray images. The use of these algorithms can improve the accuracy of disease diagnosis, ultimately leading to better patient care. Further research is needed to validate the model's accuracy and effectiveness in a clinical setting and to expand its application to other diseases.

Keywords: K-nearest neighbor, mask R-CNN, random forest, support vector machine

Procedia PDF Downloads 124

Authors: Silas Webb, Joseph Hartland

Abstract:

Background: Long-term retention of patients on ART has become a major health challenge in Sub-Saharan Africa (SSA). In 2010 a systematic review of 39 papers found that 30% of patients were no longer taking their ARTs two years after starting treatment. In the same review, it was noted that there was a paucity of data as to why patients become lost to follow-up (LTFU) in SSA. This project was performed in Mulanje Mission Hospital in Malawi as part of Swindon Academy’s Global Health eSSC. The HIV prevalence for Malawi is 10.3%, one of the highest rates in the world, however prevalence soars to 18% in the Mulanje. Therefore it is essential that patients at risk of being LTFU are identified early and managed appropriately to help them continue to participate in the service. Methodology: All patients on adult antiretroviral formulations at MMH, who were classified as ‘defaulters’ (patients missing a scheduled follow up visit by more than two months) over the last 12 months were included in the study. Demographic varibales were collected from Mastercards for data analysis. A comparison group of patients currently not lost to follow up was created by using all of the patients who attended the HIV clinic between 18th-22nd July 2016 who had never defaulted from ART. Data was analysed using the chi squared (χ²) test, as data collected was categorical, with alpha levels set at 0.05. Results: Overall, 136 patients had defaulted from ART over the past 12 months at MMH. Of these, 43 patients had missing Mastercards, so 93 defaulter datasets were analysed. In the comparison group 93 datasets were also analysed and statistical analysis done using Chi-Squared testing. A higher proportion of men in the defaulting group was noted (χ²=0.034) and defaulters tended to be younger (χ²=0.052). 94.6% of patients who defaulted were taking Tenofovir, Lamivudine and Efavirenz, the standard first line ART therapy in Malawi. The mean length of time on ART was 39.0 months (RR: -22.4-100.4) in the defaulters group and 47.3 months (RR: -19.71-114.23) in the control group, with a mean difference of 8.3 less months in the defaulters group (χ ²=0.056). Discussion: The findings in this study echo the literature, however this review expands on that and shows the demographic for the patient at most risk of defaulting and being LTFU would be: a young male who has missed more than 4 doses of ART and is within his first year of treatment. For the hospital, this data is important at it identifies significant areas for public health focus. For instance, fear of disclosure and stigma may be disproportionately affecting younger men, so interventions can be aimed specifically at them to improve their health outcomes. The mean length of time on medication was 8.3 months less in the defaulters group, with a p-value of 0.056, emphasising the need for more intensive follow-up in the early stages of treatment, when patients are at the highest risk of defaulting.

Keywords: anti-retroviral therapy, ART, HIV, lost to follow up, Malawi

Procedia PDF Downloads 170

Authors: Larisa Gheber

Abstract:

Mitosis is an essential process by which duplicated genetic information is transmitted from mother to daughter cells. Incorrect chromosome segregation during mitosis can lead to genetic diseases, chromosome instability and cancer. This process is mediated by a dynamic microtubule-based intracellular structure, the mitotic spindle. One of the major factors that govern the mitotic spindle dynamics are the kinesin-5 biological nano motors that were believed to move unidirectionally on the microtubule filaments, using ATP hydrolysis, thus performing essential functions in mitotic spindle dynamics. Surprisingly, several reports from our and other laboratories have demonstrated that some kinesin-5 motors are bi-directional: they move in minus-end direction on the microtubules as single-molecules and can switch directionality under a number of conditions. These findings broke a twenty-five-years old dogma regarding kinesin directionality (1, 2). The mechanism of this bi-directional motility and its physiological significance remain unclear. To address this unresolved problem, we apply an interdisciplinary approach combining live cell imaging, biophysical single molecule, and structural experiments to examine the activity of these motors and their mutated variants in vivo and in vitro. Our data shows that factors such as protein phosphorylation (3, 4), motor clustering on the microtubules (5, 6) and structural elements (7, 8) regulate the bi-directional motility of kinesin motors. We also show, using Cryo-EM, that bi-directional kinesin motors obtain non-canonical microtubule binding, which is essential to their special motile properties and intracellular functions. We will discuss the implication of these findings to mechanism bi-directional motility and physiological roles in mitosis.

Keywords: mitosis, cancer, kinesin, microtubules, biochemistry, biophysics

Procedia PDF Downloads 64

Authors: Marcela De Oliveira, Marina P. Da Silva, Fernando C. G. Da Rocha, Jorge M. Santos, Jaime S. Cardoso, Paulo N. Lisboa-Filho

Abstract:

Multiple Sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by neurodegeneration, inflammation, demyelination, and axonal loss. Magnetic resonance imaging (MRI), due to the richness in the information details provided, is the gold standard exam for diagnosis and follow-up of neurodegenerative diseases, such as MS. Brain atrophy, the gradual loss of brain volume, is quite extensive in multiple sclerosis, nearly 0.5-1.35% per year, far off the limits of normal aging. Thus, the brain volume quantification becomes an essential task for future analysis of the occurrence atrophy. The analysis of MRI has become a tedious and complex task for clinicians, who have to manually extract important information. This manual analysis is prone to errors and is time consuming due to various intra- and inter-operator variability. Nowadays, computerized methods for MRI segmentation have been extensively used to assist doctors in quantitative analyzes for disease diagnosis and monitoring. Thus, the purpose of this work was to evaluate the brain volume in MRI of MS patients. We used MRI scans with 30 slices of the five patients diagnosed with multiple sclerosis according to the McDonald criteria. The computational methods for the analysis of images were carried out in two steps: segmentation of the brain and brain volume quantification. The first image processing step was to perform brain extraction by skull stripping from the original image. In the skull stripper for MRI images of the brain, the algorithm registers a grayscale atlas image to the grayscale patient image. The associated brain mask is propagated using the registration transformation. Then this mask is eroded and used for a refined brain extraction based on level-sets (edge of the brain-skull border with dedicated expansion, curvature, and advection terms). In the second step, the brain volume quantification was performed by counting the voxels belonging to the segmentation mask and converted in cc. We observed an average brain volume of 1469.5 cc. We concluded that the automatic method applied in this work can be used for the brain extraction process and brain volume quantification in MRI. The development and use of computer programs can contribute to assist health professionals in the diagnosis and monitoring of patients with neurodegenerative diseases. In future works, we expect to implement more automated methods for the assessment of cerebral atrophy and brain lesions quantification, including machine-learning approaches. Acknowledgements: This work was supported by a grant from Brazilian agency Fundação de Amparo à Pesquisa do Estado de São Paulo (number 2019/16362-5).

Keywords: brain volume, magnetic resonance imaging, multiple sclerosis, skull stripper

Procedia PDF Downloads 130

Authors: Sreeparna Majee, G. C. Shit

Abstract:

A study on targeted drug delivery is carried out in an unsteady flow of blood infused with magnetic NPs (nanoparticles) with an aim to understand the flow pattern and nanoparticle aggregation in a diseased arterial segment having stenosis. The magnetic NPs are supervised by the magnetic field which is significant for therapeutic treatment of arterial diseases, tumor and cancer cells and removing blood clots. Coupled thermal energy have also been analyzed by considering dissipation of energy because of the application of the magnetic field and the viscosity of blood. Simulation technique used to solve the mathematical model is vorticity-stream function formulations in the diseased artery. An elevation in SLP (Specific loss power) is noted in the aortic bloodstream when the agglomeration of nanoparticles is higher. This phenomenon has potential application in the treatment of hyperthermia. The study focuses on the lowering of WSS (Wall Shear Stress) with increasing particle concentration at the downstream of the stenosis which depicts the vigorous flow circulation zone. These low shear stress regions prolong the residing time of the nanoparticles carrying drugs which soaks up the LDL (Low Density Lipoprotein) deposition. Moreover, an increase in NP concentration enhances the Nusselt number which marks the increase of heat transfer from the arterial wall to the surrounding tissues to destroy tumor and cancer cells without affecting the healthy cells. The results have a significant influence in the study of medicine, to treat arterial diseases such as atherosclerosis without the need for surgery which can minimize the expenditures on cardiovascular treatments.

Keywords: magnetic nanoparticles, blood flow, atherosclerosis, hyperthermia

Procedia PDF Downloads 123

Authors: Padma Chutoo, Elena Kulinskaya, Ilyas Bakbergenuly, Nicholas Steel, Dmitri Pchejetski

Abstract:

Transient ischaemic attacks (TIAs) are warning signs for future strokes. TIA patients are at increased risk of stroke and cardio-vascular events after a first episode. A majority of studies on TIA focused on the occurrence of these ancillary events after a TIA. Long-term mortality after TIA received only limited attention. We undertook this study to determine the long-term hazards of all-cause mortality following a first episode of a TIA using anonymised electronic health records (EHRs). We used a retrospective case-control study using electronic primary health care records from The Health Improvement Network (THIN) database. Patients born prior to or in year 1960, resident in England, with a first diagnosis of TIA between January 1986 and January 2017 were matched to three controls on age, sex and general medical practice. The primary outcome was all-cause mortality. The hazards of all-cause mortality were estimated using a time-varying Weibull-Cox survival model which included both scale and shape effects and a random frailty effect of GP practice. 20,633 cases and 58,634 controls were included. Cases aged 39 to 60 years at the first TIA event had the highest hazard ratio (HR) of mortality compared to matched controls (HR = 3.04, 95% CI (2.91 - 3.18)). The HRs for cases aged 61-70 years, 71-76 years and 77+ years were 1.98 (1.55 - 2.30), 1.79 (1.20 - 2.07) and 1.52 (1.15 - 1.97) compared to matched controls. Aspirin provided long-term survival benefits to cases. Cases aged 39-60 years on aspirin had HR of 0.93 (0.84 - 1.00), 0.90 (0.82 - 0.98) and 0.88 (0.80 - 0.96) at 5 years, 10 years and 15 years, respectively, compared to cases in the same age group who were not on antiplatelets. Similar beneficial effects of aspirin were observed in other age groups. There were no significant survival benefits with other antiplatelet options. No survival benefits of antiplatelet drugs were observed in controls. Our study highlights the excess long-term risk of death of TIA patients and cautions that TIA should not be treated as a benign condition. The study further recommends aspirin as the better option for secondary prevention for TIA patients compared to clopidogrel recommended by NICE guidelines. Management of risk factors and treatment strategies should be important challenges to reduce the burden of disease.

Keywords: dual antiplatelet therapy (DAPT), General Practice, Multiple Imputation, The Health Improvement Network(THIN), hazard ratio (HR), Weibull-Cox model

Procedia PDF Downloads 131

Authors: Ilija Kelepurovski, Stefan Lazorovski, Pece Petkovski, Marian Anakievski, Svetlana Petkovska

Abstract:

Introduction: Benign prostatic hyperplasia (BPH) is a common condition that affects men over the age of 50 and is characterized by an enlarged prostate gland that can cause lower urinary tract symptoms (LUTS). Uroflowmetry and cystoscopy are two commonly used diagnostic tests to evaluate LUTS and diagnose BPH. While both tests can be useful, there is a risk of overusing cystoscopy and underusing uroflowmetry in the evaluation of LUTS. The aim of this study was to compare the use of uroflowmetry and cystoscopy in a prospective cohort of 100 patients with suspected BPH or other urinary tract conditions and to assess the diagnostic yield of each test. Materials and Methods: This was a prospective study of 100 male patients over the age of 50 with suspected BPH or other urinary tract conditions who underwent uroflowmetry and cystoscopy for the evaluation of LUTS at a single tertiary care center. Inclusion criteria included male patients over the age of 50 with suspected BPH or other urinary tract conditions, while exclusion criteria included previous urethral or bladder surgery, active urinary tract infection, and significant comorbidities. The primary outcome of the study was the frequency of cystoscopy in the evaluation of LUTS, and the secondary outcome was the diagnostic yield of each test. Results: Of the 100 patients included in the study, 86 (86%) were diagnosed with BPH and 14 (14%) had other urinary tract conditions. The mean age of the study population was 67 years. Uroflowmetry was performed on all 100 patients, while cystoscopy was performed on 70 (70%) of the patients. The diagnostic yield of uroflowmetry was high, with a clear diagnosis made in 92 (92%) of the patients. The diagnostic yield of cystoscopy was also high, with a clear diagnosis made in 63 (90%) of the patients who underwent the procedure. There was no statistically significant difference in the diagnostic yield of uroflowmetry and cystoscopy (p = 0.20). Discussion: Our study found that uroflowmetry is an effective and well-tolerated diagnostic tool for evaluating LUTS and diagnosing BPH, with a high diagnostic yield and low risk of complications. Cystoscopy is also a useful diagnostic tool, but it is more invasive and carries a small risk of complications such as bleeding or urinary tract infection. Both tests had a high diagnostic yield, suggesting that either test can provide useful information in the evaluation of LUTS. However, the fact that 70% of the study population underwent cystoscopy raises concerns about the potential overuse of this test in the evaluation of LUTS. This is especially relevant given the focus on patient-centered care and the need to minimize unnecessary or invasive procedures. Our findings underscore the importance of considering the clinical context and using evidence-based guidelines. Conclusion: In this prospective study of 100 patients with suspected BPH or other urinary tract conditions, we found that uroflowmetry and cystoscopy were both valuable diagnostic tools for the evaluation of LUTS. However, the potential overuse of cystoscopy in this population warrants further investigation and highlights the need for careful consideration of the optimal use of diagnostic tests in the evaluation of LUTS and the diagnosis of BPH. Further research is needed to better understand the relative roles of uroflowmetry and cystoscopy in the diagnostic workup of patients with LUTS, and to develop evidence-based guidelines for their appropriate use.

Keywords: uroflowmetry, cystoscopy, LUTS, BPH

Procedia PDF Downloads 62

Authors: Walid Al-Qerem, Ruba Zumot

Abstract:

Background: The rise of obesity among children and adolescents remains a primary challenge for healthcare providers globally and in the Middle East. The aim of the present study is to determine the prevalence of obesity among 5-20 years old Jordanians based on CDC criteria. Method: A total of 5722 Jordanians (37% males; 63% females) aged 5-20 years data were retrieved from the Jordanian Ministry of Health electronic database (Hakeem). As per the CDC selection criteria, the chosen data pertains exclusively to healthy Jordanian children and adolescents who are medically sound, not suffering from health conditions, and not undergoing any treatments that could hinder normal growth patterns, such as severe infection, chronic kidney disease (CKD), Down’s syndrome, attention deficit hyperactivity disorder, cancer, heart disease, lung disease, cystic fibrosis, Crohn’s disease, type 1 diabetes, hormonal disturbances, any stress-related conditions, hormonal therapy such as corticosteroids, Growth hormones (GHS) or gonadotropin-releasing hormone agonists, insulin, and amphetamines or any other stimulants. In addition, participants with missing or invalid data values for anthropometric measurements were excluded from the study. Weight for age and body mass index for age were analyzed comparatively for Jordanian children and adolescents against the international growth standards. The Z-score for each record was computed based on CDC equations. As per CDC classifications, BMI for age percentiles, values ≥85th and < 95th are classified as overweight, and value at ≥ 95th is classified as obesity. Results: The average age of the evaluated sample was 12.33 ±4.39 years (10.79 ±3.39 for males and 13.23 ± 4.66 for females). The mean weight for males and females were 33.16±14.17 Kg and 133.54±17.17 cm for males, 43.86 ±18.82 Kg, and 142.19±18.35 for females, while for BMI the mean was for boys and girls 17.81±3.88 and 20.52±5.03 respectively. The results indicated that based on CDC criteria, 8.9% of males were classified as children/adolescents with overweight, and 9.7% were classified as children/adolescents with obesity, while in females, 17.8% were classified as children/adolescents with overweight and 10.2% were classified as children/adolescents with obesity. Discussion: The high prevalence of obesity reported in the present study emphasizes the importance of applying different strategies to prevent childhood obesity, including encouraging physical activity, promoting healthier food options, and behavioral changes. Conclusion: The results presented in this study indicated the high prevalence of overweight/obesity among Jordanian adolescents and children, which must be tagged by healthcare planners and providers.

Keywords: CDC, obesity, childhood, Jordan

Procedia PDF Downloads 40

Authors: Heru Al Amin

Abstract:

Sarcoidosis is a granulomatous inflammatory disorder of unclear etiology that can affect multiple different organ systems. Isolated cardiac sarcoidosis is a very rare condition that causes lethal arrhythmia and heart failure. A definite diagnosis of cardiac sarcoidosis remains challenging. The use of multimodality imaging plays a pivotal role in the diagnosis of this entity. Case summary: In this report, we discuss a case of a 50-year-old woman who presented with recurrent palpitation, dizziness, vertigo and presyncope. Electrocardiogram revealed variable heart blocks, including first-degree AV block, second-degree AV block, high-degree AV block, complete AV block, trifascicular block and sometimes supraventricular arrhythmia. Twenty-four hours of Holter monitoring show atrial bigeminy, first-degree AV block and trifascicular block. Transthoracic echocardiography showed Thinning of basal anteroseptal and inferred septum with LV dilatation with reduction of Global Longitudinal Strain. A dual-chamber pacemaker was implanted. CT Coronary angiogram showed no coronary artery disease. Cardiac magnetic resonance revealed basal anteroseptal and inferior septum thinning with focal edema with LGE suggestive of sarcoidosis. Computed tomography of the chest showed no lymphadenopathy or pulmonary infiltration. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) of the whole body showed. We started steroids and followed up with the patient. Conclusion: This case serves to highlight the challenges in identifying and managing isolated CS in a young patient with recurrent syncope with variable heart block. Early, even late initiation of steroids can improve arrhythmia as well as left ventricular function.

Keywords: cardiac sarcoidosis, conduction abnormality, syncope, cardiac MRI

Procedia PDF Downloads 73

Authors: Khaled M. Ali, Ayman A. Mostafa, Soliman M. Soliman

Abstract:

Objectives: To describe the most common clinical and endoscopic findings associated with complicated corneal ulcers in cats, and to determine the short-term outcomes after surgical treatment of these cats. Animals Eighteen client-owned cats of different breeds (52 females and 28 males), ranging in age from 3 months to 6 years, with corneal ulcers. Procedures: Cats were clinically evaluated to initially determine the concurrent corneal abnormalities. Endoscopic examination was performed to determine the anterior and posterior segments abnormalities. Superficial and deep stromal ulcers were treated using conjunctival flap. Corneal sequestrum was treated by partial keratectomy and conjunctival flap. Anterior synechia was treated via peripheral iridectomy and separation of the adhesion between the iris and the inner cornea. Symblepharon was treated by removal of the adhered conjunctival membrane from the cornea. Incurable endophthalmitis was treated surgically by extirpation. Short-term outcomes after surgical managements of selected corneal abnormalities were then assessed clinically and endoscopically. Results: Deep stromal ulcer with descemetocele, endophthalmitis, symblepharon, corneal sequestration and anterior synechia with secondary glaucoma and corneal scarring were the most common complications of corneal ulcer. FHV-1 was a common etiologic factor of corneal ulceration. Persistent corneal scars of varying shape and size developed in cats with deep stromal ulcer, anterior synechia, and corneal sequestration. Conclusions: Domestic shorthaired and Persian cats were the most predisposed breeds to FHV-1 infection and subsequent corneal ulceration. Immediate management of patients with corneal ulcer would prevent serious complications. No age or sex predisposition to complicated corneal ulceration in cats.

Keywords: cats, complicated corneal ulceration, clinical, endoscopic diagnosis, FHV-1

Procedia PDF Downloads 268

Authors: Gordon Weight, Hermione Tsoi, Patrick Cutinha, Sanjay Rajpal

Abstract:

Aim: Greenlight-laser prostatectomy (GLLP) is becoming a popular treatment option for bladder outlet obstruction and lower urinary tract symptoms (LUTS). In this retrospective study, we aim to explore the patient selection, perioperative morbidity, and functional outcomes of GLLP. Methods: Patients who underwent GLLP at a UK tertiary centre between June 2018 and November 2021 were included in this study. Retrospective data covering patient demographics, perioperative parameters and postoperative outcomes were collected using the electronic records systems. Results: 305 patients were included in this study with a mean age of 73 (range 30-90) years. The most common indication (62.6%) for the procedure was patient’s wish to be free from long-term catheters (LTC) or intermittent catheterisation (ISC), followed by failed medical therapy for LUTS (36.4%). 84.6% of patients had an ASA ≥2, and 32.1% took anticoagulant or antiplatelet therapy. Inpatient stays were minimal, with the majority (68.2%) of patients were performed as day case, and only 10.5% of patients requiring more than a single night admission. The 3-month readmission rate was 10.8%, with the most common causes being haematuria and urinary-tract infection. The successful TWOC rate at follow up was 91.2%. Amongst the 19 patients who failed TWOC, 14 had LTC prior to the procedure and 4 had been performing ISC. Conclusions: Our study shows that GLLP is a safe and effective day case treatment and can be suitable for elderly and comorbid patients. Patients requiring LTC or ISC pre-operatively should be counselled carefully about the risk of not being catheter-free post procedure.

Keywords: urology, endourology, prostate, bladder outlet obstruction, laser

Procedia PDF Downloads 54

Authors: Khadeeja Munawar, Shamsul Haque

Abstract:

The claim that traumatic events influence the recalled memories and mental health has received mixed empirical support. This study examines the memories of a sample drawn from Pakistan, a country that has witnessed many life-changing socio-political events, wars, and natural disasters in 72 years of its history. A sample of 210 senior citizens (Mage = 64.35, SD = 6.33) was recruited from Pakistan. The aim was to investigate if participants retrieved more memories related to past traumatic events using a word-cueing technique. Each participant reported ten memories to ten neutral cue words. The results revealed that past traumatic events were not adversely affecting the memories and mental health of participants. When memories were plotted with respect to the ages at which the events happened, a pronounced bump at 11-20 years of age was seen. Memories within as well as outside of the bump were mostly positive. The multilevel logistic regression modelling showed that the memories recalled were personally important and played a role in enhancing resilience. The findings revealed that despite facing an array of ethnic, religious, political, economic, and social conflicts, the participants were resilient, recalled predominantly positive memories, and had intact mental health. The findings have clinical implications in Cognitive Behavioral Therapy (CBT). The patients can be made aware of their negative emotions, troublesome/traumatic memories, and the distorted thinking patterns and their memories can be restructured. The findings can also be used to teach Memory Specificity Training (MEST) by psycho-educating the patients around changes in memory functioning and enhancing the recall of memories, which are more specific, vivid, and filled with sensory details.

Keywords: cognitive behavioral therapy, memories, mental health, resilience, trauma

Procedia PDF Downloads 136

Authors: Vadim A. Kuznetsov, Anna M. Soldatova, Tatyana N. Enina, Elena A. Gorbatenko, Dmitrii V. Krinochkin

Abstract:

The aim of the study was to evaluate potential parameters related with super-response to CRT. Methods: 60 CRT patients (mean age 54.3 ± 9.8 years; 80% men) with congestive heart failure (CHF) II-IV NYHA functional class, left ventricular ejection fraction < 35% were enrolled. At baseline, 1 month, 3 months and each 6 months after implantation clinical, electrocardiographic and echocardiographic parameters, NT-proBNP level were evaluated. According to the best decrease of left ventricular end-systolic volume (LVESV) (mean follow-up period 33.7 ± 15.1 months) patients were classified as super-responders (SR) (n=28; reduction in LVESV ≥ 30%) and non-SR (n=32; reduction in LVESV < 30%). Results: At baseline groups differed in age (58.1 ± 5.8 years in SR vs 50.8 ± 11.4 years in non-SR; p=0.003), gender (female gender 32.1% vs 9.4% respectively; p=0.028), width of QRS complex (157.6 ± 40.6 ms in SR vs 137.6 ± 33.9 ms in non-SR; p=0.044). Percentage of LBBB was equal between groups (75% in SR vs 59.4% in non-SR; p=0.274). All parameters of mechanical dyssynchrony were higher in SR, but only difference in left ventricular pre-ejection period (LVPEP) was statistically significant (153.0 ± 35.9 ms vs. 129.3 ± 28.7 ms p=0.032). NT-proBNP level was lower in SR (1581 ± 1369 pg/ml vs 3024 ± 2431 pg/ml; p=0.006). The survival rates were 100% in SR and 90.6% in non-SR (log-rank test P=0.002). Multiple logistic regression analysis showed that LVPEP (HR 1.024; 95% CI 1.004–1.044; P = 0.017), baseline NT-proBNP level (HR 0.628; 95% CI 0.414–0.953; P=0.029) and age at baseline (HR 1.094; 95% CI 1.009-1.168; P=0.30) were independent predictors for CRT super-response. ROC curve analysis demonstrated sensitivity 71.9% and specificity 82.1% (AUC=0.827; p < 0.001) of this model in prediction of super-response to CRT. Conclusion: Super-response to CRT is associated with better survival in long-term period. Presence of LBBB was not associated with super-response. LVPEP, NT-proBNP level, and age at baseline can be used as independent predictors of CRT super-response.

Keywords: cardiac resynchronisation therapy, superresponse, congestive heart failure, left bundle branch block

Procedia PDF Downloads 378

Authors: Sara Przetocka, Krzysztof Żak, Grzegorz Dubin, Tadeusz Holak

Abstract:

Toll-like receptors (TLRs) play central role in the innate immune response and inflammation by recognizing pathogen-associated molecular patterns (PAMPs). A fundamental basis of TLR signalling is dependent upon the recruitment and association of adaptor molecules that contain the structurally conserved Toll/interleukin-1 receptor (TIR) domain. MyD88 (myeloid differentiation primary response gene 88) is the universal adaptor for TLRs and cooperates with Mal (MyD88 adapter-like protein, also known as TIRAP) in TLR4 response which is predominantly used in inflammation, host defence and carcinogenesis. Up to date two possible models of MyD88, Mal and TLR4 interactions have been proposed. The aim of our studies is to confirm or abolish presented models and accomplish the full structural characterisation of TIR domains interaction. Using molecular cloning methods we obtained several construct of MyD88 and Mal TIR domain with GST or 6xHis tag. Gel filtration method as well as pull-down analysis confirmed that recombinant TIR domains from MyD88 and Mal are binding in complexes. To examine whether obtained complexes are homo- or heterodimers we carried out cross-linking reaction of TIR domains with BS3 compound combined with mass spectrometry. To investigate which amino acid residues are involved in this interaction the NMR titration experiments were performed. 15N MyD88-TIR solution was complemented with non-labelled Mal-TIR. The results undoubtedly indicate that MyD88-TIR interact with Mal-TIR. Moreover 2D spectra demonstrated that simultaneously Mal-TIR self-dimerization occurs which is necessary to create proper scaffold for Mal-TIR and MyD88-TIR interaction. Final step of this study will be crystallization of MyD88 and Mal TIR domains complex. This crystal structure and characterisation of its interface will have an impact in understanding the TLR signalling pathway and possibly will be used in development of new anti-cancer treatment.

Keywords: cancer, MyD88, TIR domains, Toll-like receptors

Procedia PDF Downloads 277

Authors: Larissa Burruano, Sergey Grabovyj, Irina Nguen

Abstract:

The study aimed to assess the level of adherence to anti retroviral therapy (ART) and to examine the relationship between adherence and risk behavior factor (drug use) among patients infected with HIV. The patients with newly diagnosed or established HIV infection under follow-up at the Sumskij Regional Centre for AIDS Prevention in Ukraine were eligible for this study. Medical records were used to measure the patient’s adherence to medication. Measurements were obtained at month 6 and at month 12 to calculate the number of medication omission during the past 30 days: (on a 2-point scale – once until three in a month – were considered adherent, three and more in a month – were considered non-adherent). Of the 50 study participants, 27 (54.0%) were men and 23 (46.0%) women. The mean age is 35.2 years (SD= 5.1). A majority of the patients (82.0%) is in the age group of 25-30 years. The main level of adherence was 74.0% and 66.0% at 6 and 12 months, respectively. The main routes of HIV transmission were drug injection among men 12 (44.4%) and sexual contact among women 11 (47.8%). Univariate analyses indicated that patients who had lower level of education were more likely to have been non-adherent at month 6- (X2 =5.1, n=50, p < .05) and at month 12 (X2 = 4.34, n=50, p < .05). Multivariate tests showed that only age (OR= 1.163 [95% CI 0.98–1.370]) was significant independent predictor of treatment adherence, while gender, education, employment status were not predictive for the risk of developing non-compliance. There was not a significant interaction between non-adherence and intravenous drug use. Consistent with these findings, younger people were more likely to have missed a dose of their medication because they had a greater sense of invulnerability than older patients. The study indicates that the socio demographic characteristic should be taken into an account in the future research regarding adherence in the case of HIV infection. If the patient anti retroviral adherence can be improved by qualitatively better medical care in all regions of the Ukraine, behavioral changes in the population can to be expected in the long term.

Keywords: HIV, antiretroviral therapy, adherence, Ukraine, Eastern Europe

Procedia PDF Downloads 275

Authors: Meral Tuncbilek, Duygu Sac, Irem Durmaz, Rengul Cetin Atalay

Abstract:

Nucleoside analogs are a pharmacologically diverse family that includes cytotoxic compounds, antiviral agents, and immunosuppressive molecules. Purine nucleoside derivatives such as fludarabine, cladribine, and pentostatin are significant drugs used in chemotherapy for the treatment of solid tumors and hematological malignancies. In this study, we synthesized novel purine ribonucleoside analogs containing a 4-(4-substituted phenylsulfonyl) piperazine in the substituent at N6- and O-substituted sulfonyl group at 5’-position as putative cytotoxic agents. The newly obtained compounds were then characterized for their cytotoxicity in human cancer cell lines. The 5’, 6-disubstituted 9-(β-D-ribofuranosyl)purine derivatives (44-67) were readily obtained from commercially available inosine in seven steps in very cost effective synthesis approach. The newly synthesized compounds were first evaluated for their anti-tumor activities against human liver (Huh7), colon (HCT116) and breast (MCF7) carcinoma cell lines. The IC50 values were in micromolar concentrations with 5’, 6-disubstituted purine nucleoside derivatives. Time-dependent IC50 values for each molecule were also calculated in comparison with known cytotoxic agents Camptothecin (CPT), 5-Fluorouracil (5-FU), Cladribine, Pentostatine and Fludarabine. N6-(4-trifluoromethyl phenyl) / N6-(4-bromophenyl) and 5’-O-(4-methoxybenzene sulfonyl) / 5’-O-(benzenesulfonyl) derivatives 54, 64 displayed the best cytotoxic activity with IC50 values of 8.8, 7 µM against MCF7 cell line. The N6-(4-methylphenyl) analog 50 was also very active (IC50= 10.7 μM) against HCT116 cell line. Furthermore, compound 64 had a better cytotoxic activity than the known cell growth inhibitors 5-FU and Fludarabine on Huh7 (1.5 vs 30.7, 29.9 μM for 5-FU and Fludarabine).

Keywords: cytotoxic activity, Huh7, HCT116, MCF7, nucleoside, synthesis

Procedia PDF Downloads 231

Authors: K. Rawojć, J. Miszczyk, A. Możdżeń, A. Panek, J. Swakoń, M. Rydygier

Abstract:

Due to the mitotic delay, poor mitotic index and disappearance of lymphocytes from peripheral blood circulation, assessing the DNA damage after high dose exposure is less effective. Conventional chromosome aberration analysis or cytokinesis-blocked micronucleus assay do not provide an accurate dose estimation or radiosensitivity prediction in doses higher than 6.0 Gy. For this reason, there is a need to establish reliable methods allowing analysis of biological effects after exposure in high dose range i.e., during particle radiotherapy. Lately, Premature Chromosome Condensation (PCC) has become an important method in high dose biodosimetry and a promising treatment modality to cancer patients. The aim of the study was to evaluate the usefulness of drug-induced PCC scoring procedure in an experimental mode, where 100 G2/M cells were analyzed in different dose ranges. To test the consistency of obtained results, scoring was performed by 3 independent persons in the same mode and following identical scoring criteria. Whole-body exposure was simulated in an in vitro experiment by irradiating whole blood collected from healthy donors with 60 MeV protons and 250 keV X-rays, in the range of 4.0 – 20.0 Gy. Drug-induced PCC assay was performed on human peripheral blood lymphocytes (HPBL) isolated after in vitro exposure. Cells were cultured for 48 hours with PHA. Then to achieve premature condensation, calyculin A was added. After Giemsa staining, chromosome spreads were photographed and manually analyzed by scorers. The dose-effect curves were derived by counting the excess chromosome fragments. The results indicated adequate dose estimates for the whole-body exposure scenario in the high dose range for both studied types of radiation. Moreover, compared results revealed no significant differences between scores, which has an important meaning in reducing the analysis time. These investigations were conducted as a part of an extended examination of 60 MeV protons from AIC-144 isochronous cyclotron, at the Institute of Nuclear Physics in Kraków, Poland (IFJ PAN) by cytogenetic and molecular methods and were partially supported by grant DEC-2013/09/D/NZ7/00324 from the National Science Centre, Poland.

Keywords: cell response to radiation exposure, drug induced premature chromosome condensation, premature chromosome condensation procedure, proton therapy

Procedia PDF Downloads 336

Authors: M. G. Talasbayen, N. N. Dyussenbayev, Y. D. Kali, R. A. Zholbarysov, Y. N. Duissenbayev, I. Z. Mammadinova, S. M. Nuradilov

Abstract:

Background. Hemorrhagic stroke is an acute cerebrovascular accident resulting from rupture of a cerebral vessel or increased permeability of the wall and imbibition of blood into the brain parenchyma. Arterial hypertension is a common cause of hemorrhagic stroke. Male gender and age over 55 years is a risk factor for intracerebral hemorrhage. Treatment of intracerebral hemorrhage is aimed at the primary pathophysiological link: the relief of coagulopathy and the control of arterial hypertension. Early surgical treatment can limit cerebral compression; prevent toxic effects of blood to the brain parenchyma. Despite progress in the development of neuroimaging data, the use of minimally invasive techniques, and navigation system, mortality from intracerebral hemorrhage remains high. Materials and methods. The study included 78 patients (62.82% male and 37.18% female) with a verified diagnosis of hemorrhagic stroke in the period from 2019 to 2021. The age of patients ranged from 25 to 80 years, the average age was 54.66±11.9 years. Demographic, brain CT data (localization, volume of hematomas), methods of treatment, and disease outcome were analyzed. Results. The retrospective analyze demonstrate that 78.2% of all patients underwent surgical treatment: decompressive craniectomy in 37.7%, craniotomy with hematoma evacuation in 29.5%, and hematoma draining in 24.59% cases. The study of the proportion of deaths, depending on the volume of intracerebral hemorrhage, shows that the number of deaths was higher in the group with a hematoma volume of more than 60 ml. Evaluation of the relationship between the time before surgery and mortality demonstrates that the most favorable outcome is observed during surgical treatment in the interval from 3 to 24 hours. Mortality depending on age did not reveal a significant difference between age groups. An analysis of the impact of the surgery type on mortality reveals that decompressive craniectomy with or without hematoma evacuation led to an unfavorable outcome in 73.9% of cases, while craniotomy with hematoma evacuation and drainage led to mortality only in 28.82% cases. Conclusion. Even though the multimodal approaches, the development of surgical techniques and equipment, and the selection of optimal conservative therapy, the question of determining the tactics of managing and treating hemorrhagic strokes is still controversial. Nevertheless, our experience shows that surgical intervention within 24 hours from the moment of admission and craniotomy with hematoma evacuation improves the prognosis of treatment outcomes.

Keywords: hemorragic stroke, Intracerebral hemorrhage, surgical treatment, stroke mortality

Procedia PDF Downloads 94

Authors: Nizar Ghali, Bernard Fortin, Guy Lacroix

Abstract:

In Quebec, colonoscopies volumes have continued to rise in recent years in the absence of effective monitoring mechanism for the appropriateness and the quality of these exams. In 2010, November, Quebec Government introduced the colorectal cancer-screening program in the objective to control for volume and cost imperfection. This program is based on clinical standards and was initiated for first group of institutions. One year later, Government adds financial incentives for participants institutions. In this analysis, we want to assess for the causal effect of the two components of this program: clinical pathways and financial incentives. Especially we assess for the reform effect on healthcare quality and population health in the context that medical remuneration is not directly dependent on this additional funding offered by the program. We have data on admissions episodes and deaths for 8 years. We use multistate model analog to difference in difference approach to estimate reform effect on the transition probability between different states for each patient. Our results show that the reform reduced length of stay without deterioration in hospital mortality or readmission rate. In the other hand, the program contributed to decrease the hospitalization rate and a less invasive treatment approach for colorectal surgeries. This is a sign of healthcare quality and population health improvement. We demonstrate in this analysis that physicians’ behavior can be affected by both clinical standards and financial incentives even if offered to facilities.

Keywords: multi-state and multi-episode transition model, healthcare quality, length of stay, transition probability, difference in difference

Procedia PDF Downloads 200

Authors: Cecilia Moreira, Rita Paiva, Daniela Macedo, Leonor Ribeiro, Isabel Fernandes, Luis Costa

Abstract:

Background: Head and neck paragangliomas are a rare group of tumors with a large spectrum of clinical manifestations. The approach to evaluate and treat these lesions has evolved over the last years. Surgery was the standard for the approach of these patients, but nowadays new techniques of imaging and radiation therapy changed that paradigm. Despite advances in treating, the growth potential and clinical outcome of individual cases remain largely unpredictable. Objectives: Characterization of our institutional experience with clinical management of these tumors. Methods: This was a cross-sectional study of patients followed in our institution between 01 January and 31 December 2017 with paragangliomas of the head and neck and cranial base. Data on tumor location, catecholamine levels, and specific imaging modalities employed in diagnostic workup, treatment modality, tumor control and recurrence, complications of treatment and hereditary status were collected and summarized. Results: A total of four female patients were followed between 01 January and 31 December 2017 in our institution. The mean age of our cohort was 53 (± 16.1) years. The primary locations were at the level of the tympanic jug (n=2, 50%) and carotid body (n=2, 50%), and only one of the tumors of the carotid body presented pulmonary metastasis at the time of diagnosis. None of the lesions were catecholamine-secreting. Two patients underwent genetic testing, with no mutations identified. The initial clinical presentation was variable highlighting the decrease of visual acuity and headache as symptoms present in all patients. In one of the cases, loss of all teeth of the lower jaw was the presenting symptomatology. Observation with serial imaging, surgical extirpation, radiation, and stereotactic radiosurgery were employed as treatment approaches according to anatomical location and resectability of lesions. As post-therapeutic sequels the persistence of tinnitus and disabling pain stands out, presenting one of the patients neuralgia of the glossopharyngeal. Currently, all patients are under regular surveillance with a median follow up of 10 months. Conclusion: Ultimately, clinical management of these tumors remains challenging owing to heterogeneity in clinical presentation, the existence of multiple treatment alternatives, and potential to cause serious detriment to critical functions and consequently interference with the quality of life of the patients.

Keywords: clinical outcomes, head and neck, management, paragangliomas

Procedia PDF Downloads 129

Authors: Khadija Rafi, Neha Jamil, Laiba Khalid, Meerub Nawaz, Mahwish Farooq

Abstract:

Speech articulation is a complex process to produce intelligible sounds with the help of precise movements of various structures within the vocal tract. All these structures in the vocal tract are named as articulators, which comprise lips, teeth, tongue, and palate. These articulators work together to produce a range of distinct phonemes, which happen to be the basis of language. It starts with the airstream from the lungs passing through the trachea and into oral and nasal cavities. When the air passes through the mouth, the tongue and the muscles around it form such coordination it creates certain sounds. It can be seen when the tongue is placed in different positions- sometimes near the alveolar ridge, soft palate, roof of the mouth or the back of the teeth which end up creating unique qualities of each phoneme. We can articulate vowels with open vocal tracts, but the height and position of the tongue is different every time depending upon each vowel, while consonants can be pronounced when we create obstructions in the airflow. For instance, the alphabet ‘b’ is a plosive and can be produced only by briefly closing the lips. Articulation disorders can not only affect communication but can also be a hurdle in speech production. To improve articulation skills for such individuals, doctors often recommend speech therapy, which involves various kinds of exercises like jaw exercises and tongue twisters. However, this disorder is more common in children who are going through developmental articulation issues right after birth, but in adults, it can be caused by injury, neurological conditions, or other speech-related disorders. In short, speech articulation is an essential aspect of productive communication, which also includes coordination of the specific articulators to produce different intelligible sounds, which are a vital part of spoken language.

Keywords: linguistics, speech articulation, speech therapy, language learning

Procedia PDF Downloads 47

Authors: Swati Kapoor, Rajeev Upreti, Monica Mahajan, Abhaya Indrayan, Dinesh Srivastava

Abstract:

Enteric Fever is caused by gram negative bacilli Salmonella typhi and paratyphi. It is associated with high morbidity and mortality worldwide. Timely initiation of treatment is a crucial step for prevention of any complications. Cultures of body fluids are diagnostic, but not always conclusive or practically feasible in most centers. Moreover, the results of cultures delay the treatment initiation. Serological tests lack diagnostic value. The blood counts can offer a promising option in diagnosis. A retrospective study to find out the relevance of leucopenia and eosinopenia was conducted on 203 culture proven enteric fever patients and 159 culture proven non-enteric fever patients in a tertiary care hospital in New Delhi. The patient details were retrieved from the electronic medical records section of the hospital. Absolute eosinopenia was considered as absolute eosinophil count (AEC) of less than 40/mm³ (normal level: 40-400/mm³) using LH-750 Beckman Coulter Automated machine. Leucopoenia was defined as total leucocyte count (TLC) of less than 4 X 10⁹/l. Blood cultures were done using BacT/ALERT FA plus automated blood culture system before first antibiotic dose was given. Case and control groups were compared using Pearson Chi square test. It was observed that absolute eosinophil count (AEC) of 0-19/mm³ was a significant finding (p < 0.001) in enteric fever patients, whereas leucopenia was not a significant finding (p=0.096). Using Receiving Operating Characteristic (ROC) curves, it was observed that patients with both AEC < 14/mm³ and TCL < 8 x 10⁹/l had 95.6% chance of being diagnosed as enteric fever and only 4.4% chance of being diagnosed as non-enteric fever. This result was highly significant with p < 0.001. This is a very useful association of AEC and TLC found in enteric fever patients of this study which can be used for the early initiation of treatment in clinically suspected enteric fever patients.

Keywords: absolute eosinopenia, absolute eosinophil count, enteric fever, leucopenia, total leucocyte count

Procedia PDF Downloads 161

Authors: Tamphasana Wairokpam

Abstract:

Inflammatory myopathies (IMs) have long been recognised as a heterogenous family of myopathies with acute, subacute, and sometimes chronic presentation and are potentially treatable. Necrotizing autoimmune myopathies (NAM) are a relatively new subset of myopathies. Patients generally present with subacute onset of proximal myopathy and significantly elevated creatinine kinase (CK) levels. It is being increasingly recognised that there are limitations to the independent diagnostic utility of muscle biopsy. Immunohistochemistry tests may reveal important information in these cases. The traditional classification of IMs failed to recognise NAM as a separate entity and did not adequately emphasize the diversity of IMs. This review and case report on NAM aims to highlight the heterogeneity of this entity and focus on the distinct clinical presentation, biopsy findings, specific auto-antibodies implicated, and available treatment options with prognosis. This article is a meta-analysis of literatures on NAM and a case report illustrating the clinical course, investigation and biopsy findings, antibodies implicated, and management of a patient with NAM. The main databases used for the search were Pubmed, Google Scholar, and Cochrane Library. Altogether, 67 publications have been taken as references. Two biomarkers, anti-signal recognition protein (SRP) and anti- hydroxyl methylglutaryl-coenzyme A reductase (HMGCR) Abs, have been found to have an association with NAM in about 2/3rd of cases. Interestingly, anti-SRP associated NAM appears to be more aggressive in its clinical course when compared to its anti-HMGCR associated counterpart. Biopsy shows muscle fibre necrosis without inflammation. There are reports of statin-induced NAM where progression of myopathy has been seen even after discontinuation of statins, pointing towards an underlying immune mechanism. Diagnosisng NAM is essential as it requires more aggressive immunotherapy than other types of IMs. Most cases are refractory to corticosteroid monotherapy. Immunosuppressive therapy with other immunotherapeutic agents such as IVIg, rituximab, mycophenolate mofetil, azathioprine has been explored and found to have a role in the treatment of NAM. In conclusion,given the heterogeneity of NAM, it appears that NAM is not just a single entity but consists of many different forms, despite the similarities in presentation and its classification remains an evolving field. A thorough understanding of underlying mechanism and the clinical correlation with antibodies associated with NAM is essential for efficacious management and disease prognostication.

Keywords: inflammatory myopathies, necrotising autoimmune myopathies, anti-SRP antibody, anti-HMGCR antibody, statin induced myopathy

Procedia PDF Downloads 94

Authors: Chi-Ching Lee, Po-Jung Huang, Kuo-Yang Huang, Petrus Tang

Abstract:

Background: Recent advances in high-throughput research technologies such as new-generation sequencing and multi-dimensional liquid chromatography makes it possible to dissect the complete transcriptome and proteome in a single run for the first time. However, it is almost impossible for many laboratories to handle and analysis these “BIG” data without the support from a bioinformatics team. We aimed to provide a web-based analysis platform for users with only limited knowledge on bio-computing to study the functional genomics and proteomics. Method: We use NCI-60 as an example dataset to demonstrate the power of the web-based analysis platform and data delivering system: C-eXpress takes a simple text file that contain the standard NCBI gene or protein ID and expression levels (rpkm or fold) as input file to generate a distribution map of gene/protein expression levels in a heatmap diagram organized by color gradients. The diagram is hyper-linked to a dynamic html table that allows the users to filter the datasets based on various gene features. A dynamic summary chart is generated automatically after each filtering process. Results: We implemented an integrated database that contain pre-defined annotations such as gene/protein properties (ID, name, length, MW, pI); pathways based on KEGG and GO biological process; subcellular localization based on GO cellular component; functional classification based on GO molecular function, kinase, peptidase and transporter. Multiple ways of sorting of column and rows is also provided for comparative analysis and visualization of multiple samples.

Keywords: cancer, visualization, database, functional annotation

Procedia PDF Downloads 603

Authors: Rajesh Ranjan, Marimuthu Palaniswami, A. A. Hashmi

Abstract:

With the changing lifestyle and environment around us, the prevalence of the critical and incurable disease has proliferated. One such condition is the neurological disorder which is rampant among the old age population and is increasing at an unstoppable rate. Most of the neurological disorder patients suffer from some movement disorder affecting the movement of their body parts. Tremor is the most common movement disorder which is prevalent in such patients that infect the upper or lower limbs or both extremities. The tremor symptoms are commonly visible in Parkinson’s disease patient, and it can also be a pure tremor (essential tremor). The patients suffering from tremor face enormous trouble in performing the daily activity, and they always need a caretaker for assistance. In the clinics, the assessment of tremor is done through a manual clinical rating task such as Unified Parkinson’s disease rating scale which is time taking and cumbersome. Neurologists have also affirmed a challenge in differentiating a Parkinsonian tremor with the pure tremor which is essential in providing an accurate diagnosis. Therefore, there is a need to develop a monitoring and assistive tool for the tremor patient that keep on checking their health condition by coordinating them with the clinicians and caretakers for early diagnosis and assistance in performing the daily activity. In our research, we focus on developing a system for automatic classification of tremor which can accurately differentiate the pure tremor from the Parkinsonian tremor using a wearable accelerometer-based device, so that adequate diagnosis can be provided to the correct patient. In this research, a study was conducted in the neuro-clinic to assess the upper wrist movement of the patient suffering from Pure (Essential) tremor and Parkinsonian tremor using a wearable accelerometer-based device. Four tasks were designed in accordance with Unified Parkinson’s disease motor rating scale which is used to assess the rest, postural, intentional and action tremor in such patient. Various features such as time-frequency domain, wavelet-based and fast-Fourier transform based cross-correlation were extracted from the tri-axial signal which was used as input feature vector space for the different supervised and unsupervised learning tools for quantification of severity of tremor. A minimum covariance maximum correlation energy comparison index was also developed which was used as the input feature for various classification tools for distinguishing the PT and ET tremor types. An automatic system for efficient classification of tremor was developed using feature extraction methods, and superior performance was achieved using K-nearest neighbors and Support Vector Machine classifiers respectively.

Keywords: machine learning approach for neurological disorder assessment, automatic classification of tremor types, feature extraction method for tremor classification, neurological movement disorder, parkinsonian tremor, essential tremor

Procedia PDF Downloads 141

Authors: C. M. Williams, R. English, P. King, I. M. Brown

Abstract:

Introduction: Pseudoangiomatous Stromal Hyperplasia (PASH) is a benign fibrous proliferation of breast stroma affecting predominantly premenopausal women with no significant increased risk of breast cancer. Informal recommendations for management have continued to evolve over recent years from surgical excision to observation, although there are no specific national guidelines. This study assesses the safety of a non-surgical approach to PASH management by review of cases at a single centre. Methods: Retrospective case series review (January 2011 – August 2016) was conducted on consecutive PASH cases. Diagnostic classification (clinical, radiological and histological), management outcomes, and breast cancer incidence were recorded. Results: 43 patients were followed up for median of 25 months (3-64) with 75% symptomatic at presentation. 12% of cases (n=5) had a radiological score (BIRADS MMG or US) ≥ 4 of which 3 were confirmed malignant. One further malignancy was detected and proven radiologically occult and contralateral. No patients were diagnosed with a malignancy during follow-up. Treatment evolved from 67% surgical in 2011 to 33% in 2016. Conclusions: The management of PASH has transitioned in line with other published experience. The preliminary findings suggest this appears safe with no evidence of missed malignancies; however, longer follow up is required to confirm long-term safety. Recommendations: PASH with suspicious radiological findings ( ≥ U4/R4) warrants multidisciplinary discussion for excision. In the absence of histological or radiological suspicion of malignancy, PASH can be safely managed without surgery.

Keywords: benign breast disease, conservative management, malignancy, pseudoangiomatous stromal hyperplasia, surgical excision

Procedia PDF Downloads 116

Authors: Sree Bash Chandra Debnath, Didier Tonneau, Carole Fauquet, Agnes Tallet, Julien Darreon

Abstract:

Purpose: Inorganic scintillating dosimetry is the most recent promising technique to solve several dosimetric issues and provide quality assurance in radiation therapy. Despite several advantages, the major issue of using scintillating detectors is the Cerenkov effect, typically induced in the visible emission range. In this context, the purpose of this research work is to evaluate the performance of a novel infrared inorganic scintillator detector (IR-ISD) in the radiation therapy treatment to ensure Cerenkov free signal and the best matches between the delivered and prescribed doses during treatment. Methods: A simple and small-scale infrared inorganic scintillating detector of 100 µm diameter with a sensitive scintillating volume of 2x10-6 mm3 was developed. A prototype of the dose verification system has been introduced based on PTIR1470/F (provided by Phosphor Technology®) material used in the proposed novel IR-ISD. The detector was tested on an Elekta LINAC system tuned at 6 MV/15MV and a brachytherapy source (Ir-192) used in the patient treatment protocol. The associated dose rate was measured in count rate (photons/s) using a highly sensitive photon counter (sensitivity ~20ph/s). Overall measurements were performed in IBATM water tank phantoms by following international Technical Reports series recommendations (TRS 381) for radiotherapy and TG43U1 recommendations for brachytherapy. The performance of the detector was tested through several dosimetric parameters such as PDD, beam profiling, Cerenkov measurement, dose linearity, dose rate linearity repeatability, and scintillator stability. Finally, a comparative study is also shown using a reference microdiamond dosimeter, Monte-Carlo (MC) simulation, and data from recent literature. Results: This study is highlighting the complete removal of the Cerenkov effect especially for small field radiation beam characterization. The detector provides an entire linear response with the dose in the 4cGy to 800 cGy range, independently of the field size selected from 5 x 5 cm² down to 0.5 x 0.5 cm². A perfect repeatability (0.2 % variation from average) with day-to-day reproducibility (0.3% variation) was observed. Measurements demonstrated that ISD has superlinear behavior with dose rate (R2=1) varying from 50 cGy/s to 1000 cGy/s. PDD profiles obtained in water present identical behavior with a build-up maximum depth dose at 15 mm for different small fields irradiation. A low dimension of 0.5 x 0.5 cm² field profiles have been characterized, and the field cross profile presents a Gaussian-like shape. The standard deviation (1σ) of the scintillating signal remains within 0.02% while having a very low convolution effect, thanks to lower sensitive volume. Finally, during brachytherapy, a comparison with MC simulations shows that considering energy dependency, measurement agrees within 0.8% till 0.2 cm source to detector distance. Conclusion: The proposed scintillating detector in this study shows no- Cerenkov radiation and efficient performance for several radiation therapy measurement parameters. Therefore, it is anticipated that the IR-ISD system can be promoted to validate with direct clinical investigations, such as appropriate dose verification and quality control in the Treatment Planning System (TPS).

Keywords: IR-Scintillating detector, dose measurement, micro-scintillators, Cerenkov effect

Procedia PDF Downloads 167

Authors: Wu Liching

Abstract:

Aim This case aims to discuss the pathogenesis, clinical manifestations and medical treatment of strokes caused by mitochondrial gene mutations. Methods Diagnosis of ischemic stroke caused by mitochondrial gene defect by means of "next-generation sequencing mitochondrial DNA gene variation detection", imaging examination, neurological examination, and medical history; this study took samples from the neurology ward of a medical center in northern Taiwan cases diagnosed with acute cerebral infarction as the research objects. Result This case is a 49-year-old married woman with a rare disease, mitochondrial gene mutation inducing ischemic stroke. She has severe hearing impairment and needs to use hearing aids, and has a history of diabetes. During the patient’s hospitalization, the blood test showed that serum Lactate: 7.72 mmol/L, Lactate (CSF) 5.9 mmol/L. Through the collection of relevant medical history, neurological evaluation showed changes in consciousness and cognition, slow response in language expression, and brain magnetic resonance imaging examination showed subacute bilateral temporal lobe infarction, which was an atypical type of stroke. The lineage DNA gene has m.3243A>G known pathogenic mutation point, and its heteroplasmic level is 24.6%. This pathogenic point is located in MITOMAP and recorded as Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) , Leigh Syndrome and other disease-related pathogenic loci, this mutation is located in ClinVar and recorded as Pathogenic (dbSNP: rs199474657), so it is diagnosed as a case of stroke caused by a rare disease mitochondrial gene mutation. After medical treatment, there was no more seizure during hospitalization. After interventional rehabilitation, the patient's limb weakness, poor language function, and cognitive impairment have all improved significantly. Conclusion Mitochondrial disorders can also be associated with abnormalities in psychological, neurological, cerebral cortical function, and autonomic functions, as well as problems with internal medical diseases. Therefore, the differential diagnoses cover a wide range and are not easy to be diagnosed. After neurological evaluation, medical history collection, imaging and rare disease serological examination, atypical ischemic stroke caused by rare mitochondrial gene mutation was diagnosed. We hope that through this case, the diagnosis of rare disease mitochondrial gene variation leading to cerebral infarction will be more familiar to clinical medical staff, and this case report may help to improve the clinical diagnosis and treatment for patients with similar clinical symptoms in the future.

Keywords: acute stroke, MELAS, lactic acidosis, mitochondrial disorders

Procedia PDF Downloads 56

Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

Abstract:

Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

Procedia PDF Downloads 74