Search results for: cancer surgery

Authors: Adriana C. Panayi, Riaz A. Agha, Brady A. Sieber, Dennis P. Orgill

Abstract:

Background: Increased rates of both breast cancer and obesity have resulted in more women seeking breast reconstruction. These women may be at increased risk for perioperative complications. A systematic review was conducted to assess the outcomes in obese women who have undergone breast reconstruction following mastectomy. Methods: Cochrane, PUBMED and EMBASE electronic databases were screened and data was extracted from included studies. The clinical outcomes assessed were surgical complications, medical complications, length of postoperative hospital stay, reoperation rate and patient satisfaction. Results: 33 studies met the inclusion criteria for the review and 29 provided enough data to be included in the meta-analysis (71368 patients, 20061 of which were obese). Obese women were 2.3 times more likely to experience surgical complications (95 percent CI 2.19 to 2.39; P < 0.00001), 2.8 times more likely to have medical complications (95 percent CI 2.41 to 3.26; P < 0.00001) and had a 1.9 times higher risk of reoperation (95 percent CI 1.75 to 2.07; P < 0.00001). The most common complication, wound dehiscence, was 2.5 times more likely in obese women (95 percent CI 1.80 to 3.52; P < 0.00001). Sensitivity analysis confirmed that obese women were more likely to experience surgical complications (RR 2.36, 95% CI 2.22–2.52; P < 0.00001). Conclusions: This study provides evidence that obesity increases the risk of complications in both implant and autologous reconstruction. Additional prospective and observational studies are needed to determine if weight reduction prior to reconstruction reduces the perioperative risks associated with obesity.

Keywords: autologous reconstruction, breast cancer, breast reconstruction, literature review, obesity, oncology, prosthetic reconstruction

Procedia PDF Downloads 308

Authors: Ravi Kiran Pothamsetty, Radha Rani Ghosh, Baby Paul Thaliath

Abstract:

Radiation therapy has undergone many advancements and evloved from 2D to 3D. Recently, with rapid pace of drug discoveries, cutting edge technology, and clinical trials has made innovative advancements in computer technology and treatment planning and upgraded to intensity modulated radiotherapy (IMRT) which delivers in homogenous dose to tumor and normal tissues. The present study was a hospital-based experience comparing two different conformal radiotherapy techniques for brain tumors. This analytical study design has been conducted at Regional Cancer Centre, India from January 2014 to January 2015. Ten patients have been selected after inclusion and exclusion criteria. All the patients were treated on Artiste Siemens Linac Accelerator. The tolerance level for maximum dose was 6.0 Gyfor lenses and 54.0 Gy for brain stem, optic chiasm and optical nerves as per RTOG criteria. Mean and standard deviation values of PTV98%, PTV 95% and PTV 2% in IMRT were 93.16±2.9, 95.01±3.4 and 103.1±1.1 respectively; for 3DCRT were 91.4±4.7, 94.17±2.6 and 102.7±0.39 respectively. PTV max dose (%) in IMRT and 3D-CRT were 104.7±0.96 and 103.9±1.0 respectively. Maximum dose to the tumor can be delivered with IMRT with acceptable toxicity limits. Variables such as expertise, location of tumor, patient condition, and TPS influence the outcome of the treatment.

Keywords: brain tumors, intensity modulated radiotherapy (IMRT), three dimensional conformal radiotherapy (3D-CRT), radiation therapy oncology group (RTOG)

Procedia PDF Downloads 239

Authors: Anik Barua, Rabiul Hossain, Labonno Barua, Rashadul Hossain, Nurul Absar

Abstract:

Background: Globally, the burden of cancer is increasing consistently. Modern cancer therapies include lots of toxicity in the non-targeted organs reducing the life expectancy of the patients. Hence, scientists are trying to seek noble compounds from natural sources to treat cancer. Objectives: The objectives of the present study are to evaluate the phytochemicals, in vitro antioxidants, and in vivo and in silico anticancer study of various solvent fractions of Tinospora cordifolia (Willd.). Methodology: In this experiment, standard quantitative and qualitative assay methods were used to analyze the phytochemicals. The antioxidant activity was measured using the DPPH and ABTS scavenging methods. The in vivo antitumor activity is evaluated against Ehrlich ascites carcinoma (EAC) cell bearing in Swiss albino mice. In-silico ADME/T and molecular docking study were performed to assess the potential of stated phytochemicals against Transcription Factor STAT3b/DNA Complex of adenocarcinoma. Findings: Phytochemical screening confirmed the presence of flavonoids, alkaloids, glycosides, tannins, and carbohydrates. A significant amount of phenolic (20.19±0.3 mg/g GAE) and flavonoids (9.46±0.18 mg/g GAE) were found in methanolic extract in quantitative screening. Tinospora cordifolia methanolic extract showed promising DPPH and ABTS scavenging activity with the IC50 value of 1222.99 µg/mL and 1534.34 µg/mL, respectively, which was concentration dependent. In vivo anticancer activity in EAC cell-bearing mice showed significant (P < 0.05) percent inhibition of cell growth (60.12±1.22) was found at the highest dose compared with standard drug 5-Fluorouracil (81.18±1.28). Forty-two phytochemicals exhibit notable pharmacokinetics properties and passed drug-likeness screening tests in silico. In molecular docking study, (25S)-3Beta-acetoxy-5-alpha-22-beta-spirost-9(11)-en-12-beta-ol showed docking score (-8.5 kJ/mol) with significant non-bonding interactions with target enzyme. Conclusions: The results were found to be significant and confirmed that the methanolic extract of Tinospora cordifolia has remarkable antitumor activity with antioxidant potential. The Tinospora cordifolia methanolic extract may be considered a potent anticancer agent for advanced research.

Keywords: anticancer, antioxidant, Tinospora cordifolia, EAC cell

Procedia PDF Downloads 129

Authors: Darshana Rathod, Kirtikumar Rathod, Kamlesh Kumari, Abhilasha Motghare

Abstract:

Background and Aims: Hypospadias is one of the common congenital anomalies in males. Various modalities are used for pain management, including caudal, penile, pudendal, ring blocks, and systemic analgesics. There has yet to be a consensus regarding the most effective and safe analgesic method for controlling pain in these children. We planned this study to determine our institute's pain management practices for hypospadias surgeries. Material and Methods: This retrospective cohort study reviewed 150 children with hypospadias undergoing surgery from January 2020 to December 2023. Data regarding the mode of pain management, postoperative opioid requirement, PACU discharge, and complications was collected from the records. Results: For postoperative pain, 33 (22%) children received caudal block, 60 (40%) penile block, and 57 (38%) were managed by intravenous analgesics. A significant difference was found in the three groups, with the IV analgesic group requiring significantly higher opioid boluses in PACU [43 (75.4%) required two boluses (p < 0.05)]. The difference in PACU discharge time among the three groups was statistically significant (p< 0.05), with IV analgesics groups having the highest (55 mins [47, 60]), the Caudal group at 35mins (30, 40), and the dorsal penile block group at 35mins (25, 40). There was no significant difference in complications like edema, meatal stenosis, urethra-cutaneous fistula, or wound dehiscence among all three groups. Conclusion: Intravenous analgesics and regional blocks like caudal and penile blocks are the common pain management modalities in our institute. The regional blocks are effective in managing pain in the postoperative period and are not significantly associated with complications.

Keywords: caudal block, hypospadias, pain management, penile block

Procedia PDF Downloads 45

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

Abstract:

The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

Procedia PDF Downloads 110

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

Abstract:

Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

Procedia PDF Downloads 274

Authors: Mona Isazad Mashinchi, Davood Roshan Sangachin, Francis J. Sullivan, Dietrich Rebholz-Schuhmann

Abstract:

Background: Decision-making processes are nowadays driven by data, data analytics and Business Intelligence (BI). BI as a software platform can provide a wide variety of capabilities such as organization memory, information integration, insight creation and presentation capabilities. Visualizing data through dashboards is one of the BI solutions (for a variety of areas) which helps managers in the decision making processes to expose the most informative information at a glance. In the healthcare domain to date, dashboard presentations are more frequently used to track performance related metrics and less frequently used to monitor those quality parameters which relate directly to patient outcomes. Providing effective and timely care for patients and improving the health outcome are highly dependent on presenting and visualizing data and information. Objective: In this research, the focus is on the presentation capabilities of BI to design a dashboard for prostate cancer (PC) data that allows better decision making for the patients, the hospital and the healthcare system related to a cancer dataset. The aim of this research is to customize a retrospective PC dataset in a dashboard interface to give a better understanding of data in the categories (risk factors, treatment approaches, disease control and side effects) which matter most to patients as well as other stakeholders. By presenting the outcome in the dashboard we address one of the major targets of a value-based health care (VBHC) delivery model which is measuring the value and presenting the outcome to different actors in HC industry (such as patients and doctors) for a better decision making. Method: For visualizing the stored data to users, three interactive dashboards based on the PC dataset have been developed (using the Tableau Software) to provide better views to the risk factors, treatment approaches, and side effects. Results: Many benefits derived from interactive graphs and tables in dashboards which helped to easily visualize and see the patients at risk, better understanding the relationship between patient's status after treatment and their initial status before treatment, or to choose better decision about treatments with fewer side effects regarding patient status and etc. Conclusions: Building a well-designed and informative dashboard is related to three important factors including; the users, goals and the data types. Dashboard's hierarchies, drilling, and graphical features can guide doctors to better navigate through information. The features of the interactive PC dashboard not only let doctors ask specific questions and filter the results based on the key performance indicators (KPI) such as: Gleason Grade, Patient's Age and Status, but may also help patients to better understand different treatment outcomes, such as side effects during the time, and have an active role in their treatment decisions. Currently, we are extending the results to the real-time interactive dashboard that users (either patients and doctors) can easily explore the data by choosing preferred attribute and data to make better near real-time decisions.

Keywords: business intelligence, dashboard, decision making, healthcare, prostate cancer, value-based healthcare

Procedia PDF Downloads 141

Authors: Ugo Galvanetto, Pirto G. Pavan, Mirco Zaccariotto

Abstract:

The discipline of Computer-integrated surgery (CIS) will provide equipment able to improve the efficiency of healthcare systems and, which is more important, clinical results. Surgeons and machines will cooperate in new ways that will extend surgeons’ ability to train, plan and carry out surgery. Patient specific CIS of the brain requires several steps: 1 - Fast generation of brain models. Based on image recognition of MR images and equipped with artificial intelligence, image recognition techniques should differentiate among all brain tissues and segment them. After that, automatic mesh generation should create the mathematical model of the brain in which the various tissues (white matter, grey matter, cerebrospinal fluid …) are clearly located in the correct positions. 2 – Reliable and fast simulation of the surgical process. Computational mechanics will be the crucial aspect of the entire procedure. New algorithms will be used to simulate the mechanical behaviour of cutting through cerebral tissues. 3 – Real time provision of visual and haptic feedback A sophisticated human-machine interface based on ergonomics and psychology will provide the feedback to the surgeon. The present work will address in particular point 2. Modelling the cutting of soft tissue in a structure as complex as the human brain is an extremely challenging problem in computational mechanics. The finite element method (FEM), that accurately represents complex geometries and accounts for material and geometrical nonlinearities, is the most used computational tool to simulate the mechanical response of soft tissues. However, the main drawback of FEM lies in the mechanics theory on which it is based, classical continuum Mechanics, which assumes matter is a continuum with no discontinuity. FEM must resort to complex tools such as pre-defined cohesive zones, external phase-field variables, and demanding remeshing techniques to include discontinuities. However, all approaches to equip FEM computational methods with the capability to describe material separation, such as interface elements with cohesive zone models, X-FEM, element erosion, phase-field, have some drawbacks that make them unsuitable for surgery simulation. Interface elements require a-priori knowledge of crack paths. The use of XFEM in 3D is cumbersome. Element erosion does not conserve mass. The Phase Field approach adopts a diffusive crack model instead of describing true tissue separation typical of surgical procedures. Modelling discontinuities, so difficult when using computational approaches based on classical continuum Mechanics, is instead easy for novel computational methods based on Peridynamics (PD). PD is a non-local theory of mechanics formulated with no use of spatial derivatives. Its governing equations are valid at points or surfaces of discontinuity, and it is, therefore especially suited to describe crack propagation and fragmentation problems. Moreover, PD does not require any criterium to decide the direction of crack propagation or the conditions for crack branching or coalescence; in the PD-based computational methods, cracks develop spontaneously in the way which is the most convenient from an energy point of view. Therefore, in PD computational methods, crack propagation in 3D is as easy as it is in 2D, with a remarkable advantage with respect to all other computational techniques.

Keywords: computational mechanics, peridynamics, finite element, biomechanics

Procedia PDF Downloads 80

Authors: Kheireddine El-Boubbou

Abstract:

Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC₅₀ values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

Procedia PDF Downloads 229

Authors: Kamila Duś-Szachniewicz, Kinga M. Walaszek, Paweł Skiba, Paweł Kołodziej, Piotr Ziółkowski

Abstract:

Cell adhesion is of fundamental importance in the cell communication, signaling, and motility, and its dysfunction occurs prevalently during cancer progression. The knowledge of the molecular and cellular processes involved in abnormalities in cancer cells adhesion has greatly increased, and it has been focused mainly on cellular adhesion molecules (CAMs) and tumor microenvironment. Unfortunately, most of the data regarding CAMs expression relates to study on cells maintained in standard oxygen condition of 21%, while the emerging evidence suggests that culturing cells in ambient air is far from physiological. In fact, oxygen in human tissues ranges from 1 to 11%. The aim of this study was to compare the effects of physiological lymph node normoxia (5% O2), and hyperoxia (21% O2) on the expression of cellular adhesion molecules of primary diffuse large B-cell lymphoma cells (DLBCL) isolated from 10 lymphoma patients. Quantitative RT-PCR and immunohistochemistry were used to confirm the differential expression of several CAMs, including ICAM, CD83, CD81, CD44, depending on the level of oxygen. Our findings also suggest that DLBCL cells maintained at ambient O2 (21%) exhibit reduced growth rate and migration ability compared to the cells growing in normoxia conditions. Taking into account all the observations, we emphasize the need to identify the optimal human cell culture conditions mimicking the physiological aspects of tumor growth and differentiation.

Keywords: adhesion molecules, diffuse large B-cell lymphoma, physiological normoxia, quantitative RT-PCR

Procedia PDF Downloads 278

Authors: Harish Rajak, Kamlesh Raghuwanshi

Abstract:

Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

Procedia PDF Downloads 307

Authors: Allulu Yousef Alturki, Raghad Abdullah Alshafi, Sara Abdulaziz Alghashem, Sahar Saleh Alghamdi, Rasha Saad Suliman, Zeyad Alehaideb, Rizwan Ali

Abstract:

Cancer is recognized as a worldwide public health concern. Therefore, there is a continuous quest to discover new effective medications with less side-effects. In recent years, researchers have shown an increased interest in medicinal plants as several plant species have shown promising biological activities. Thus, we seek to investigate three medicinal herbs that are commonly-found in the Middle Easternregion and yet have not been explored in depth, including plants belonging to the Rhamnaceae, Polygonaceae, and Apocynaceaeplant families. Initially, we investigated using three types of cancer cell lines for breast, colorectal, and liver cancers. We performed high Content Imaging (HCI)-Apoptosis Assay and ApoTox-Glo™ Triplex Assay on KAIMRC2 and HCT8 cell lines. The highest activity of HCI-Apoptosis Assay was with Calligonumcomosum and Ziziphusnummularia in ethanol, followed by Calotropis procera and Ziziphusnummularia in ethyl acetate. The IC50values for the families of Rhamnaceae, Polygonaceae, and Apocynaceae in HepG2 and HCT8 cell lines ranged from 0.089 to 9.84mg/mL and 0.080to 15.08mg/mL, respectively. Further screening was conducted on an additional two cell lines, namely the MDA-MB-231 and KAIMRC2, for selected seven extracts with the highest activity having IC50values ranged from 0.058 to0.51mg/mL and 0.029 to0.19mg/mL, respectively. Continuous scientific investigations to isolate and characterize the potent bioactive phytochemical(s) are warranted. Funding: The authors acknowledge financial support from King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia. Institutional Review Board Statement: The study was approved by the Institutional Review Board of the Institutional Review Board of King Abdullah International Medical Research Center (SP21R/463/12, 24 January 2022). Acknowledgments: The authors want to express their gratitude to the College of Pharmacy (COP) at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) and King Abdullah International Medical Research Center (KAIMRC) for their continued support.

Keywords: rhamnaceae, polygonaceae, apocynaceae, natural products

Procedia PDF Downloads 115

Authors: Gabrielle O'Donoghue

Abstract:

Background: Pre-operative radiographs facilitate assessment and treatment planning in minor oral surgery. Quality assurance for dental radiography advocates the As Low As Reasonably Achievable (ALARA) principle in collecting accurate diagnostic information. Aims: To audit the quality of digital intraoral periapicals (IOPAs) taken prior to dental extractions in a metropolitan general dental practice setting. Standards: The National Radiological Protection Board (NRPB) guidance outlines three grades of radiograph quality: excellent (Grade 1 > 70% of total exposures), diagnostically acceptable (Grade 2 <20%), and unacceptable (Grade 3 <10%). Methodology: A study of pre-operative radiographs taken prior to dental extractions across 12 private general dental practices in a large metropolitan area by 44 practitioners. A total of 725 extractions were assessed, allowing 258 IOPAs to be reviewed in one audit cycle. Results: First cycle: Of 258 IOPAs: 223(86.4%) scored Grade 1, 27(10.5%) Grade 2, and 8(3.1%) Grade 3. The standard was met. 35 dental extractions were performed without an available pre-operative radiograph. Action Plan & Recommendations: Results were distributed to all staff and a continuous professional development evening organized to outline recommendations to improve image quality. A second audit cycle is proposed at a six-month interval to review the recommendations and appraise results. Conclusion: The overall standard of radiographs met the published guidelines. A significant improvement in the number of procedures undertaken without pre-operative imaging is expected at a six-month interval period. An investigation into undiagnostic imaging and associated adverse patient outcomes is being considered. Maintenance of the standards achieved is predicted in the second audit cycle to ensure consistent high quality imaging.

Keywords: audit, oral radiology, oral surgery, periapical radiographs, quality assurance

Procedia PDF Downloads 166

Authors: Fossarello Maurizio, Mattana Giorgio, Tatti Filippo.

Abstract:

The most widely performed surgical procedure in Open-Angle Glaucoma (OAG) is trabeculectomy. Although this filtering procedure is extremely effective, surgical failure and postoperative complications are reported. Due to the its invasive nature and possible complications, trabeculectomy is usually reserved, in practice, for patients who are refractory to medical and laser therapy. Recently, a number of micro-invasive surgical techniques (MIGS: Micro-Invasive Glaucoma Surgery), have been introduced in clinical practice. They meet the criteria of micro-incisional approach, minimal tissue damage, short surgical time, reliable IOP reduction, extremely high safety profile and rapid post-operative recovery. Xen45 Gel Implant (Allergan, Dublin, Ireland) is one of the MIGS alternatives, and consists in a porcine gelatin tube designed to create an aqueous flow from the anterior chamber to the subconjunctival space, bypassing the resistance of the trabecular meshwork. In this study we report the results of this technique as a favorable option in the treatment of OAG for its benefits in term of efficacy and safety, either alone or in combination with cataract surgery. This is a retrospective, single-center study conducted in consecutive OAG patients, who underwent Xen45 Gel Stent implantation alone or in combination with phacoemulsification, from October 2018 to June 2019. The primary endpoint of the study was to evaluate the reduction of both IOP and number of antiglaucoma medications at 12 months. The secondary endpoint was to correlate filtering bleb morphology evaluated by means of anterior segment OCT with efficacy in IOP lowering and eventual further procedures requirement. Data were recorded on Microsoft Excel and study analysis was performed using Microsoft Excel and SPSS (IBM). Mean values with standard deviations were calculated for IOPs and number of antiglaucoma medications at all points. Kolmogorov-Smirnov test showed that IOP followed a normal distribution at all time, therefore the paired Student’s T test was used to compare baseline and postoperative mean IOP. Correlation between postoperative Day 1 IOP and Month 12 IOP was evaluated using Pearson coefficient. Thirty-six eyes of 36 patients were evaluated. As compared to baseline, mean IOP and the mean number of antiglaucoma medications significantly decreased from 27,33 ± 7,67 mmHg to 16,3 ± 2,89 mmHg (38,8% reduction) and from 2,64 ± 1,39 to 0,42 ± 0,8 (84% reduction), respectively, at 12 months after surgery (both p < 0,001). According to bleb morphology, eyes were divided in uniform group (n=8, 22,2%), subconjunctival separation group (n=5, 13,9%), microcystic multiform group (n=9, 25%) and multiple internal layer group (n=14, 38,9%). Comparing to baseline, there was no significative difference in IOP between the 4 groups at month 12 follow-up visit. Adverse events included bleb function decrease (n=14, 38,9%), hypotony (n=8, 22,2%) and choroidal detachment (n=2, 5,6%). All eyes presenting bleb flattening underwent needling and MMC injection. The higher percentage of patients that required secondary needling was in the uniform group (75%), with a significant difference between the groups (p=0,03). Xen45 gel stent, either alone or in combination with phacoemulsification, provided a significant lowering in both IOP and medical antiglaucoma treatment and an elevated safety profile.

Keywords: anterior segment OCT, bleb morphology, micro-invasive glaucoma surgery, open angle glaucoma, Xen45 gel implant

Procedia PDF Downloads 141

Authors: Kazeem Adesina Dauda, Waheed Babatunde Yahya

Abstract:

To design a tree that maximizes within-node homogeneity, there is a need for a homogeneity measure that is appropriate for event history data with multiple risks. We consider the use of Deviance and Modified Cox-Snell residuals as a measure of impurity in Classification Regression Tree (CART) and compare our results with the results of Fiona (2008) in which homogeneity measures were based on Martingale Residual. Data structure approach was used to validate the performance of our proposed techniques via simulation and real life data. The results of univariate competing risk revealed that: using Deviance and Cox-Snell residuals as a response in within node homogeneity classification tree perform better than using other residuals irrespective of performance techniques. Bone marrow transplant data and double-blinded randomized clinical trial, conducted in other to compare two treatments for patients with prostate cancer were used to demonstrate the efficiency of our proposed method vis-à-vis the existing ones. Results from empirical studies of the bone marrow transplant data showed that the proposed model with Cox-Snell residual (Deviance=16.6498) performs better than both the Martingale residual (deviance=160.3592) and Deviance residual (Deviance=556.8822) in both event of interest and competing risks. Additionally, results from prostate cancer also reveal the performance of proposed model over the existing one in both causes, interestingly, Cox-Snell residual (MSE=0.01783563) outfit both the Martingale residual (MSE=0.1853148) and Deviance residual (MSE=0.8043366). Moreover, these results validate those obtained from the Monte-Carlo studies.

Keywords: within-node homogeneity, Martingale residual, modified Cox-Snell residual, classification and regression tree

Procedia PDF Downloads 272

Authors: Sachin Mulmi Shrestha, Xin Fang, Hui Ye, Lihua Ren, Qinghua Ji, Ruihua Shi

Abstract:

Background: Esophageal squamous cell carcinoma (ESCC) is a tumor arising from esophageal epithelial cells and is one of the major disease subtype in Asian countries, including China. Esophageal cancer is the 7th highest incidence based on the 2020 data of GLOBOCAN. The pathogenesis of cancer is still not well understood as many molecular and genetic basis of esophageal carcinogenesis has yet to be clearly elucidated. Circular RNAs are RNA molecules that are formed by back-splicing covalently joined 3′- and 5′-endsrather than canonical splicing, and recent data suggest circular RNAs could sponge miRNAs and are enriched with functional miRNA binding sites. Hence, we studied the mechanism of circular RNA, its biological function, and the relationship between microRNA in the carcinogenesis of ESCC. Methods: 4 pairs of normal and esophageal cancer tissues were collected in Zhongda hospital, affiliated to Southeast University, and high-throughput RNA sequencing was done. The result revealed that circ_0032746 was upregulated, and thus we selected circ_0032746 for further study. The backsplice junction of circRNA was validated by sanger sequence, and stability was determined by RNASE R assay. The binding site of circRNA and microRNA was predicted by circinteractome,mirandaand RNAhybrid database. Furthermore, circRNA was silenced by siRNA and then by lentivirus. The regulatory axis of circ0032746/miR4270 was validated by shRNA, mimic, and inhibitor transfection. Then, in vitro experiments were performed to assess the role of circ0032746 on proliferation (CCK-8 assay and colon formation assay), migration and invasion (Transewell assay), and apoptosis of ESCC. Results: The upregulated circ0032746 was validated in 9 pairs of tissues and 5 types of cell lines by qPCR, which showed high expression and was statistically significant (P<0.005) ). Upregulated circ0032746 was silenced by shRNA, which showed significant knockdown in KYSE 30 and TE-1 cell lines expression compared to control. Nuclear and cytoplasmic mRNA fraction experiment displayed the cytoplasmic location of circ0032746. The sponging of miR4270 was validated by co-transfection of sh-circ0032746 and mimic or inhibitor. Transfection with mimic showed the decreased expression of circ_0032746, whereas inhibitor inhibited the result. In vitro experiments showed that silencing of circ_0032746 inhibited the proliferation, migration, and invasion compared to the negative control group. The apoptosis was seen higher in a knockdown group than in the control group. Furthermore, 11 common mircoRNA target mRNAs were predicted by Targetscan, MirTarbase, and miRanda database, which may further play role in the pathogenesis. Conclusion: Our results showed that novel circ_0032746 is upregulated in ESCC and plays role in itsoncogenicity. Silencing of circ_0032746 inhibits the proliferation and migration of ESCC whereas increases the apoptosis of cancer cells. Hence, circ0032746 acts as an oncogene in ESCC by sponging with miR4270 and could be a potential biomarker in the diagnosis of ESCC in the future.

Keywords: circRNA, esophageal squamous cell carcinoma, microRNA, upregulated

Procedia PDF Downloads 113

Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

Abstract:

Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

Procedia PDF Downloads 262

Authors: Chrislaura Carmo, Luca Deiana, Mafalda Laranjo, Abilio Sobral, Armando Cordova

Abstract:

Photodynamic therapy (PDT) is currently used for the treatment of malignancies and premalignant tumors. It is based on the capture of a photosensitizing molecule (PS) which, when excited by light at a certain wavelength, reacts with oxygen and generates oxidizing species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death. BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indaceno) derivatives are emerging as important candidates for photosensitizer in photodynamic therapy of cancer cells due to their high triplet quantum yield. Today these dyes are relevant molecules in photovoltaic materials and fluorescent sensors. In this study, it will be demonstrated the possibility that BODIPY can be covalently linked to thioglycolic acid through the click reaction. Thiol−ene click chemistry has become a powerful synthesis method in materials science and surface modification. The design of biobased allyl-terminated precursors with high renewable carbon content for the construction of the thiol-ene polymer networks is essential for sustainable development and green chemistry. The work aims to synthesize the BODIPY (10-(4-(allyloxy) phenyl)-2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f] [1,3,2] diazaborinin-4-ium-5-uide) and to click reaction with Thioglycolic acid. BODIPY was synthesized by the condensation reaction between aldehyde and pyrrole in dichloromethane, followed by in situ complexation with BF3·OEt2 in the presence of the base. Then it was functionalized with allyl bromide to achieve the double bond and thus be able to carry out the click reaction. The thiol−ene click was performed using DMPA (2,2-Dimethoxy-2-phenylacetophenone) as a photo-initiator in the presence of UV light (320–500 nm) in DMF at room temperature for 24 hours. Compounds were characterized by standard analytical techniques, including UV-Vis Spectroscopy, 1H, 13C, 19F NMR and mass spectroscopy. The results of this study will be important to link BODIPY to polymers through the thiol group offering a diversity of applications and functionalization. This new molecule can be tested as third-generation photosensitizers, in which the dye is targeted by antibodies or nanocarriers by cells, mainly in cancer cells, PDT and Photodynamic Antimicrobial Chemotherapy (PACT). According to our studies, it was possible to visualize a click reaction between allyl BODIPY and thioglycolic acid. Our team will also test the reaction with other thiol groups for comparison. Further, we will do the click reaction of BODIPY with a natural polymer linked with a thiol group. The results of the above compounds will be tested in PDT assays on various lung cancer cell lines.

Keywords: bodipy, click reaction, thioglycolic acid, allyl, thiol-ene click

Procedia PDF Downloads 132

Authors: Marina S. Basta, Kirollos S. Basta

Abstract:

Cosmetic dermatology procedures have witnessed exponential growth and diversification over the last 10 years. Thus, the purpose of this study was to collect data about the latest trends for cosmetic procedures reported by dermatologists during the year 2018. This study was performed by American Society for Dermatologic Surgery (ASDS) in 2018 through sending survey invitations to 3,358 practicing dermatologists in the U.S. containing streamline questions as well as statistical questions targeted to specific analysis of cosmetic dermatology trends. Out of the targeted physicians, only 596 dermatologists reply to the survey invitation (15% overall response rate). It was noted that data collected from that survey was generalized to represent all ASDS members. Results show that there is an increase in cosmetic dermatology procedures since 12.5 million procedures were reported for 2018 compared to only 7.8 million for 2012. Injectable neuromodulators and soft tissue fillers have topped the list with a 3.7 million procedure count. Body sculpting, chemical peeling, hair transplantation, and microneedling procedures were reported to be 1.57 million cases combined. Also, the top two procedures using laser were represented in wrinkle treatment as well as sun damage correction, while the lowest two trends for laser usage were for treatments of tattoos and birthmarks. Cryolipolysis was found to be at the head of body sculpting procedures with 287,435 cases, while tumescent liposuction was reported as the least performed body sculpting procedure (18,286 cases). In conclusion, comparing the procedural trends for the last 7 years has indicated that there has been a 78% increase in soft tissue filler treatment compared to 2012. In addition, it was further noted that laser procedures scored 74% increase in the last 7 years while body contouring procedures have had four folds increase in general compared to 2012.

Keywords: cosmetic dermatology, ASDS procedure survey, laser, body sculpting

Procedia PDF Downloads 124

Authors: Hui-mei Huang, Huei-Jiun Cheng

Abstract:

Introduction Many patients are aware of the health benefits associated with an active lifestyle, but they are often hindered from engaging in physical activity due to the presence of pain. The majority of patients experience pain, which can fluctuate over time and is influenced by various factors, including gender. Gender differences in clinical pain and pain-related conditions are widely recognized. Existing literature strongly supports the notion that men and women exhibit distinct responses to pain. Previous studies conducted in Taiwan have highlighted gender differences in pain assessment, but only a limited number of studies have investigated the gender-related factors that influence pain during daily activities. The objective of this study was to examine gender differences in pain assessment among inpatients in Taiwan and investigate whether gender and surgical procedures are factors that impact the daily activities of pain. Method In this study, a prospective and structured questionnaire survey method was utilized, employing intentional sampling to gather data from inpatients admitted to a medical center in central Taiwan. The research period covered in this study is from October 1, 2019, to June 30, 2020. In this study, participants who were hospitalized within 48 hours were requested to self-assess their pain using the Numeric Rating Scale (NRS) and indicate the impact of pain on their activities. The data were analyzed to explore the potential influence of gender and surgical procedures on daily activities affected by pain. Result A total of 722 cases were included in the study, with the mean age of the subjects is 54.38 years old (SD=16.3), and the range varied from 18 to 93 years old. Among the subjects, 48.23% (n=348) were male, and 62.3% (n=450) of them had received more than 12 years of education., and 56.9% (n=411) underwent surgery. The results indicated that regardless of whether the participants underwent surgery or not, females experienced higher perceived severe pain intensity than males (t=2.248, P < .05). However, in surgical patients, there was no significant difference in gender (t=1.75, P > .05). Regarding the impact of pain on daily activities when pain intensity reached 7 , male subjects experienced a 5-point effect on their daily activities (AUC=0.84, 95% CI 0.79-0.89, P <0.01), while female subjects experienced a 7-point effect (AUC=0.88, 95% CI 0.80-0.87, P <0.01). Discussion Some studies suggest that women experience painful stimuli as more intense than men, this difference has been observed in various types of experimental pain, including mechanical and thermal stimuli. Our study reached the same conclusion, female patients exhibited greater intensity of pain. According to the research findings, The research findings highlight the significant impact of gender on individuals' response to intense pain (NRS>7) during their daily activities, with men showing a higher pain tolerance. The higher pain tolerance often observed in men may be attributed to societal conditioning, which encourages them to conceal outward expressions of pain. Further research in this area could help provide a more comprehensive understanding of the topic in Taiwan.

Keywords: pain assessment, gender, surgery, activities of daily living

Procedia PDF Downloads 75

Authors: Laila Seada, Ashraf Ibrahim, Amjad Al Shammari

Abstract:

Background and Objectives: Breast carcinoma is the most common cancer of females in Hail region, accounting for 31% of all diagnosed cancer cases followed by thyroid carcinoma (25%) and colorectal carcinoma (13%). Methods: In the present retrospective study, all cases of breast lesions received at the histopathology department in King Khalid Hospital, Hail, during the period from May 2011 to April 2016 have been retrieved from department files. For all cases, a trucut biopsy, lumpectomy, or modified radical mastectomy was available for histopathologic diagnosis, while 105/140 (75%) had, as well, preoperative fine needle aspirates (FNA). Results: 49 cases out of 140 (35%) breast lesions were carcinomas: 44/49 (89.75%) was invasive ductal, 2/49(4.1%) invasive lobular carcinomas, 1/49(2.05%) intracystic low grade papillary carcinoma and 2/49 (4.1%) ductal carcinoma in situ (DCIS). Mean age for malignant cases was 45.06 (+/-10.58): 32.6% were below the age of 40 and 30.6 below 50 years, 18.3% below 60 and 16.3% below 70 years. For the benign group, mean age was 32.52 (+/10.5) years. Benign lesions were in order of frequency: 34 fibroadenomas, 14 fibrocystic disease, 12 chronic mastitis, five granulomatous mastitis, three intraductal papillomas, and three benign phyllodes tumor. Tubular adenoma, lipoma, skin nevus, pilomatrixoma, and breast reduction specimens constituted the remaining specimens. Conclusion: Breast lesions are common in our series and invasive carcinoma accounts for more than 1/3^rd of the lumps, with 63.2% incidence in pre-menopausal ladies, below the age of 50 years. FNA as a non-invasive procedure, proved to be an effective tool in diagnosing both benign and malignant/suspicious breast lumps and should continue to be used as a first assessment line of palpable breast masses.

Keywords: age incidence, breast carcinoma, fine needle aspiration, hail region

Procedia PDF Downloads 279

Authors: Abdullah Malek, Muzn Al Khaldi, Lian Odeh, Atheer Tariq, Mohammad Al Fardan, Hiba Barqawi

Abstract:

H. pylori bacterium is a known underlying agent for gastritis, peptic ulcer disease, and gastric cancer and is believed to infect half of the world’s population. Even with the ubiquity of H. pylori bacterium, there is lack of knowledge regarding its modes of transmission, associated diseases, carcinogenic effect and means of prevention; especially in the UAE. A cross sectional study of 500 participants, of which 58% (n= 289) of the respondents were female, and 42% (n=210) were male, was conducted in Sharjah to assess the knowledge, and explore the attitudes and practices among UAE residents towards Helicobacter Pylori and its associated PUD as well as its carcinogenic nature. A structured self-administered questionnaire was distributed to the target population to establish their demographic background and selected aspects of their lifestyle. General knowledge about H. Pylori was poor, only 24.6% stated they have heard of H. pylori. Attitudes towards prevention and practices were relatively poor as well. Subjects who suffered from severe symptoms (ALARM symptoms) had significantly lower habit scores than those with mild and moderate symptoms (p=0.0078**). To the authours’ knowledge, no previous studies were conducted in the United Arab Emirates regarding the epidemiology of the infection to detect the extent of H. Pylori’s impact on the public health. The results of this study can be used to draw conclusions about the average knowledge of the UAE population regarding H. pylori. It can also be a starting point to devise new education programs and campaigns that raise awareness of this health issue which could be easily avoided with early diagnosis and antibiotic treatment.

Keywords: chronic gastritis, community health, gastric cancer, Helicobacter pylori, peptic ulcers

Procedia PDF Downloads 259

Authors: Miroslava Cuperlovic-Culf, Lipu Wang, Ketty Boyle, Nadine Makley, Ian Burton, Anissa Belkaid, Mohamed Touaibia, Marc E. Surrette

Abstract:

Metabolic changes are one of the major factors in the development of a variety of diseases in various species. Metabolism of agricultural plants is altered the following infection with pathogens sometimes contributing to resistance. At the same time, pathogens use metabolites for infection and progression. In humans, metabolism is a hallmark of cancer development for example. Quantified metabolomics data combined with other omics or clinical data and analyzed using various unsupervised and supervised methods can lead to better diagnosis and prognosis. It can also provide information about resistance as well as contribute knowledge of compounds significant for disease progression or prevention. In this work, different methods for metabolomics quantification and analysis from Nuclear Magnetic Resonance (NMR) measurements that are used for investigation of disease development in wheat and human cells will be presented. One-dimensional 1H NMR spectra are used extensively for metabolic profiling due to their high reliability, wide range of applicability, speed, trivial sample preparation and low cost. This presentation will describe a new method for metabolite quantification from NMR data that combines alignment of spectra of standards to sample spectra followed by multivariate linear regression optimization of spectra of assigned metabolites to samples’ spectra. Several different alignment methods were tested and multivariate linear regression result has been compared with other quantification methods. Quantified metabolomics data can be analyzed in the variety of ways and we will present different clustering methods used for phenotype determination, network analysis providing knowledge about the relationships between metabolites through metabolic network as well as biomarker selection providing novel markers. These analysis methods have been utilized for the investigation of fusarium head blight resistance in wheat cultivars as well as analysis of the effect of estrogen receptor and carbonic anhydrase activation and inhibition on breast cancer cell metabolism. Metabolic changes in spikelet’s of wheat cultivars FL62R1, Stettler, MuchMore and Sumai3 following fusarium graminearum infection were explored. Extensive 1D 1H and 2D NMR measurements provided information for detailed metabolite assignment and quantification leading to possible metabolic markers discriminating resistance level in wheat subtypes. Quantification data is compared to results obtained using other published methods. Fusarium infection induced metabolic changes in different wheat varieties are discussed in the context of metabolic network and resistance. Quantitative metabolomics has been used for the investigation of the effect of targeted enzyme inhibition in cancer. In this work, the effect of 17 β -estradiol and ferulic acid on metabolism of ER+ breast cancer cells has been compared to their effect on ER- control cells. The effect of the inhibitors of carbonic anhydrase on the observed metabolic changes resulting from ER activation has also been determined. Metabolic profiles were studied using 1D and 2D metabolomic NMR experiments, combined with the identification and quantification of metabolites, and the annotation of the results is provided in the context of biochemical pathways.

Keywords: metabolic biomarkers, metabolic network, metabolomics, multivariate linear regression, NMR quantification, quantified metabolomics, spectral alignment

Procedia PDF Downloads 338

Authors: Riaz A. Agha, Ishani Barai, Shivanchan Rajmohan, Seon Lee, Mohammed O. Anwar, Alex J. Fowler, Dennis P. Orgill, Douglas G. Altman

Abstract:

Introduction: Medical knowledge is growing fast. Evidence-based medicine works best if the evidence is reported well. Past studies have shown reporting quality to be lacking in the field of surgery. Reporting guidelines are an important tool for authors to optimize the reporting of their research. The objective of this study was to analyse the frequency and strength of recommendation for such reporting guidelines within surgical journals. Methods: A systematic review of the 198 journals within the Journal Citation Report 2014 (surgery category) published by Thomson Reuters was undertaken. The online guide for authors for each journal was screened by two independent groups and results were compared. Data regarding the presence and strength of recommendation to use reporting guidelines was extracted. Results: 193 journals were included (as five appeared twice having changed their name). These had a median impact factor of 1.526 (range 0.047 to 8.327), with a median of 145 articles published per journal (range 29-659), with 34,036 articles published in total over the two-year window 2012-2013. The majority (62%) of surgical journals made no mention of reporting guidelines within their guidelines for authors. Of the journals (38%) that did mention them, only 14% (10/73) required the use of all relevant reporting guidelines. The most frequently mentioned reporting guideline was CONSORT (46 journals). Conclusion: The mention of reporting guidelines within the guide for authors of surgical journals needs improvement. Authors, reviewers and editors should work to ensure that research is reported in line with the relevant reporting guidelines. Journals should consider hard-wiring adherence to them. This will allow peer-reviewers to focus on what is present, not what is missing, raising the level of scholarly discourse between authors and the scientific community and reducing frustration amongst readers.

Keywords: CONSORT, guide for authors, PRISMA, reporting guidelines, journal impact factor, citation analysis

Procedia PDF Downloads 465

Authors: Stefano Andrea Denes

Abstract:

The use of dental implants to rehabilitate edentulous patients has become a well-established and effective treatment option; however, despite its high success rate, this treatment is not free of complications. The fracture of implant body is a rare cause of failure but when it does occur it can present technical challenges. In this article, we report the complete removal of a fractured osseointegrated implant using electrosurgery and ultrasonic instrumentation. The postoperative course was uneventful, no bleeding, infection, or hematoma formation was observed.

Keywords: dental implant, oral surgery, electrosurgery, piezosurgery

Procedia PDF Downloads 270

Authors: Selim M. Khan, Dustin D. Pearson, Tryggve Rönnqvist, Markus E. Nielsen, Joshua M. Taron, Aaron A. Goodarzi

Abstract:

Accumulation of radioactive radon gas in indoor air poses a serious risk to human health by increasing the lifetime risk of lung cancer and is classified by IARC as a category one carcinogen. Radon exposure risks are a function of geologic, geographic, design, and human behavioural variables and can change over time. Using time series and deep machine learning modelling, we analyzed long-term radon test outcomes as a function of building metrics from 25,489 Canadian and 38,596 Swedish residential properties constructed between 1945 to 2020. While Canadian and Swedish properties built between 1970 and 1980 are comparable (96–103 Bq/m³), innate radon risks subsequently diverge, rising in Canada and falling in Sweden such that 21st Century Canadian houses show 467% greater average radon (131 Bq/m³) relative to Swedish equivalents (28 Bq/m³). These trends are consistent across housing types and regions within each country. The introduction of energy efficiency measures within Canadian and Swedish building codes coincided with opposing radon level trajectories in each nation. Deep machine learning modelling predicts that, without intervention, average Canadian residential radon levels will increase to 176 Bq/m³ by 2050, emphasizing the importance and urgency of future building code intervention to achieve systemic radon reduction in Canada.

Keywords: radon health risk, time-series, deep machine learning, lung cancer, Canada, Sweden

Procedia PDF Downloads 85

Authors: Bao-Fang Wen, Meng-Na Dai, Gao-Pei Zhu, Chen-Xi Zhang, Jing Sun, Xun-Bao Yin, Yu-Han Zhao, Hong-Wei Sun, Wei-Fen Zhang

Abstract:

A drug-loaded nanoparticles containing berberine hydrochloride (BH/FA-CTS-NPs) was prepared. The physicochemical characterizations of BH/FA-CTS-NPs and the inhibitory effect on the HeLa cells were investigated. Folic acid-conjugated chitosan (FA-CTS) was prepared by amino reaction of folic acid active ester and chitosan molecules; BH/FA-CTS-NPs were prepared using ionic cross-linking technique with BH as a model drug. The morphology and particle size were determined by Transmission Electron Microscope (TEM). The average diameters and polydispersity index (PDI) were evaluated by Dynamic Light Scattering (DLS). The interaction between various components and the nanocomplex were characterized by Fourier Transform Infrared Spectroscopy (FT-IR). The entrapment efficiency (EE), drug-loading (DL) and in vitro release were studied by UV spectrophotometer. The effect of cell anti-migratory and anti-invasive actions of BH/FA-CTS-NPs were investigated using MTT assays, wound healing assays, Annexin-V-FITC single staining assays, and flow cytometry, respectively. HeLa nude mice subcutaneously transplanted tumor model was established and treated with different drugs to observe the effect of BH/FA-CTS-NPs in vivo on HeLa bearing tumor. The BH/FA-CTS-NPs prepared in this experiment have a regular shape, uniform particle size, and no aggregation phenomenon. The results of DLS showed that mean particle size, PDI and Zeta potential of BH/FA-CTS NPs were (249.2 ± 3.6) nm, 0.129 ± 0.09, 33.6 ± 2.09, respectively, and the average diameter and PDI were stable in 90 days. The results of FT-IR demonstrated that the characteristic peaks of FA-CTS and BH/FA-CTS-NPs confirmed that FA-CTS cross-linked successfully and BH was encapsulated in NPs. The EE and DL amount were (79.3 ± 3.12) % and (7.24 ± 1.41) %, respectively. The results of in vitro release study indicated that the cumulative release of BH/FA-CTS NPs was (89.48±2.81) % in phosphate-buffered saline (PBS, pH 7.4) within 48h; these results by MTT assays and wund healing assays indicated that BH/FA-CTS NPs not only inhibited the proliferation of HeLa cells in a concentration and time-dependent manner but can induce apoptosis as well. The subcutaneous xenograft tumor formation rate of human cervical cancer cell line HeLa in nude mice was 98% after inoculation for 2 weeks. Compared with BH group and BH/CTS-NPs group, the xenograft tumor growth of BH/FA-CTS-NPs group was obviously slower; the result indicated that BH/FA-CTS-NPs could significantly inhibit the growth of HeLa xenograft tumor. BH/FA-CTS NPs with the sustained release effect could be prepared successfully by the ionic crosslinking method. Considering these properties, block proliferation and impairing the migration of the HeLa cell line, BH/FA-CTS NPs could be an important compound for consideration in the treatment of cervical cancer.

Keywords: folic-acid, chitosan, berberine hydrochloride, nanoparticles, cervical cancer

Procedia PDF Downloads 122

Authors: Indu Barwal, Shloka Thakur, Subhash C. Yadav

Abstract:

The plant virus capsid protein based nanoparticles are extensively studied for their application in biomedical research for development of nanomedicines and drug delivery systems. We have developed a chimeric drug delivery system by controlled in vitro assembly of separately bioconjugated fluorescent dye (as reporting molecule), folic acid (as receptor binding biomolecule for targeted delivery) and doxorubicin (as anticancer drug) using modified EDC NHS chemistry on heterologously overexpressed (E. coli) capsid proteins of cowpea chlorotic mottle virus (CCMV). This chimeric vehicle was further encapsidated on gold nanoparticles (20nm) coated with 5≠ thiolated DNA probe to neutralize the positive charge of capsid proteins. This facilitates the in vitro assembly of modified capsid subunits on the gold nanoparticles to develop chimeric GNPs encapsidated targeted drug delivery system. The bioconjugation of functionalities, number of functionality on capsid subunits as well as virus like nanoparticles, structural stability and in vitro assembly were confirmed by SDS PAGE, relative absorbance, MALDI TOF, ESI-MS, Circular dichroism, intrinsic tryptophan fluorescence, zeta particle size analyzer and TEM imaging. This vehicle was stable at pH 4.0 to 8.0 suitable for many organelles targeting. This in vitro assembled chimeric plant virus like particles could be suitable for ideal drug delivery vehicles for subcutaneous cancer treatment and could be further modified for other type of cancer treatment by conjugating other functionalities (targeting, drug) on capsids.

Keywords: chimeric drug delivery vehicles, bioconjugated plant, virus, capsid

Procedia PDF Downloads 493

Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim

Abstract:

Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.

Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion

Procedia PDF Downloads 450

Authors: Soheila Zhaeentan, Anders Von Heijne, Elisabet Hagert, André Stark, Björn Salomonsson

Abstract:

Recommended treatment for traumatic rotator cuff tear (TRCT) is surgery within a few weeks after injury if the diagnosis is made early, especially if a functional impairment of the shoulder exists. This may lead to the assumption that a poor outcome then can be expected in delayed surgical treatment, when the patient is diagnosed at a later stage. The aim of this study was to investigate if a surgical repair later than three months after injury may result in successful outcomes and patient satisfaction. There is evidence in literature that good results of treatment can be expected up to three months after the injury, but little is known of later treatment with cuff repair. 73 patients (75 shoulders), 58 males/17 females, mean age 59 (range 34-­‐72), who had undergone surgical intervention for TRCT between January 1999 to December 2011 at our clinic, were included in this study. Patients were assessed by MRI investigation, clinical examination, Western Ontario Rotator Cuff index (WORC), Oxford Shoulder Score, Constant-­‐Murley Score, EQ-­‐5D and patient subjective satisfaction at follow-­‐up. The patients treated surgically within three months ( < 12 weeks) after injury (39 cases) were compared with patients treated more than three months ( ≥ 12 weeks) after injury (36 cases). WORC was used as the primary outcome measure and the other variables as secondary. A senior consultant radiologist, blinded to patient category and clinical outcome, evaluated all MRI-­‐images. Rotator cuff integrity, presence of arthritis, fatty degeneration and muscle atrophy was evaluated in all cases. The average follow-­‐up time was 56 months (range 14-­‐149) and the average time from injury to repair was 16 weeks (range 3-­‐104). No statistically significant differences were found for any of the assessed parameters or scores between the two groups. The mean WORC score was 77 (early group, range 25-­‐ 100 and late group, range 27-­‐100) for both groups (p= 0.86), Constant-­‐Murley Score (p= 0.91), Oxford Shoulder Score (p= 0.79), EQ-­‐5D index (p= 0.86). Re-­‐tear frequency was 24% for both groups, and the patients with re-­‐tear reported less satisfaction with outcome. Discussion and conclusion: This study shows that surgical repair of TRCT performed later than three months after injury may result in good functional outcomes and patient satisfaction. However, this does not motivate an intentional delay in surgery when there is an indication for surgical repair as that delay may adversely affect the possibility to perform a repair. Our results show that surgeons may safely consider surgical repair even if a delay in diagnosis has occurred. A retrospective cohort study on 75 shoulders shows good functional result after traumatic rotator cuff tear (TRCT) treated surgically up to one year after the injury.

Keywords: traumatic rotator cuff injury, time to surgery, surgical outcome, retrospective cohort study

Procedia PDF Downloads 223