Search results for: hereditary breast-ovarian cancer syndrome

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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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

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

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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

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Authors: Naomi Sakamoto, Eisuke Fukuma, Mika Nashimoto, Yoshitomo Koshida

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Background: Selective localization of the metastatic lymph node with clip and removal of clipped nodes with sentinel lymph node (SLN), known as targeted axillary dissection (TAD), reduced false-negative rates (FNR) of SLN biopsy (SLNB) after neoadjuvant chemotherapy (NAC). For the patients who achieved nodal pathologic complete response (pCR), accurate staging of axilla by TAD lead to omit axillary lymph node dissection (ALND), decreasing postoperative arm morbidity without a negative effect on overall survival. This study aimed to investigate the ultrasound (US) identification rate and success removal rate of two kinds of ultrasound-visible clips placed in metastatic lymph nodes during TAD procedure. Methods: This prospective study was conducted using patients with clinically T1-3, N1, 2, M0 breast cancer undergoing NAC followed by surgery. A US-visible clip was placed in the suspicious lymph node under US guidance before neoadjuvant chemotherapy. Before surgery, US examination was performed to evaluate the detection rate of clipped node. During the surgery, the clipped node was removed using several localization techniques, including hook-wire localization, dye-injection, or fluorescence technique, followed by a dual-technique SLNB and resection of palpable nodes if present. For the fluorescence technique, after injection of 0.1-0.2 mL of indocyanine green dye (ICG) into the clipped node, ICG fluorescent imaging was performed using the Photodynamic Eye infrared camera (Hamamatsu Photonics k. k., Shizuoka, Japan). For the dye injection method, 0.1-0.2 mL of pyoktanin blue dye was injected into the clipped node. Results: A total of 29 patients were enrolled. Hydromark™ breast biopsy site markers (Hydromark, T3 shape; Devicor Medical Japan, Tokyo, Japan) was used in 15patients, whereas a UltraCor™ Twirl™ breast marker (Twirl; C.R. Bard, Inc, NJ, USA) was placed in 14 patients. US identified the clipped node marked with the UltraCore Twirl in 100% (14/14) and with the Hydromark in 93.3% (14/15, p = ns). Success removal of clipped node marked with the UltraCore Twirl was achieved in 100% (14/14), whereas the node marked with the Hydromark was removed in 80% (12/15) (p = ns). Conclusions: The ultrasound identification rate differed between the two types of ultrasound-visible clips, which also affected the success removal rate of clipped nodes. Labelling the positive node with a US-highly-visible clip allowed successful TAD.

Keywords: breast cancer, neoadjuvant chemotherapy, targeted axillary dissection, breast tissue marker, clip

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

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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

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Authors: Kheireddine El-Boubbou

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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

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

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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

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Authors: Kamyar Kabirifar, Majid Azarniush, Behbood Maashkar

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A proper house is a suitable residential area which provides comfort, proper accessibility, security, stability and permanence of structure, enough lighting, Proper initial infrastructures and ventilation for its inhabitants and the most important of all, it should be proportional to the family’s financial power. Saving energy and making optimal usage of it and also taking advantage of stable energies are the bases of green buildings. Making green building will help the health of a person living in it and in its surrounding. It will support the people and provoke their satisfaction. Not only it will bring about the raise of level of the quality of life for building inhabitants, but also it will cause the promotion of quality level of life of the people living in the surrounding area and the society.

Keywords: quality of life, green building, environment pollution, sick building

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Authors: Harish Rajak, Kamlesh Raghuwanshi

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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

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

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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

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Authors: David Tennison

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In the wake of the Covid-19 pandemic, a new chronic illness emerged onto the global stage: Long Covid. Long Covid presents with several symptoms commonly seen in other poorly-understood illnesses, such as fibromyalgia (FM) and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). However, while Long Covid has swiftly become a recognised illness, FM and ME/CFS are still seen as contested, which impacts patient care and healthcare experiences. This study aims to examine what the differences are between Long Covid and FM; and if the Long Covid case can provide guidance for how to address the healthcare challenge of contested illnesses. To address this question, this study performed comprehensive research into the history of FM; our current biomedical understanding of it; and available healthcare interventions (within the context of the UK NHS). Analysis was undertaken of the stigma and stereotypes around FM, and a comparison made between FM and the emerging Long Covid literature, along with the healthcare response to Long Covid. This study finds that healthcare for chronic contested illnesses in the UK is vastly insufficient - in terms of pharmaceutical and holistic interventions, and the provision of secondary care options. Interestingly, for Long Covid, many of the treatment suggestions are pulled directly from those used for contested illnesses. The key difference is in terms of funding and momentum – Long Covid has generated exponentially more interest and research in a short time than there has been in the last few decades of contested illness research. This stands to help people with FM and ME/CFS – for example, research has recently been funded into “brain fog”, a previously elusive and misunderstood symptom. FM is culturally regarded as a “women’s disease” and FM stigma stems from notions of “hysteria”. A key finding is that the idea of FM affecting women disproportionally is not reflected in modern population studies. Emerging data on Long Covid also suggests a slight leaning towards more female patients, however it is less feminised, potentially due to it emerging in the global historical moment of the pandemic. Another key difference is that FM is rated as an extremely low-prestige illness by healthcare professionals, while it was in large part due to the advocacy of affected healthcare professionals that Long Covid was so quickly recognised by science and medicine. In conclusion, Long Covid (and the risk of future pandemics and post-viral illnesses) highlight a crucial need for implementing new, and reinforcing existing, care networks for chronic illnesses. The difference in how contested illnesses like FM, and new ones like Long Covid are treated have a lot to do with the historical moment in which they emerge – but cultural stereotypes, from within and without medicine, need updating. Particularly as they contribute to disease stigma that causes genuine harm to patients. However, widespread understanding and acceptance of Long Covid could help fight contested illness stigma, and the attention, funding and research into Long Covid may actually help raise the profile of contested illnesses and uncover answers about their symptomatology.

Keywords: long COVID, fibromyalgia, myalgic encephalomyelitis, chronic fatigue syndrome, NHS, healthcare, contested illnesses, chronic illnesses, COVID-19 pandemic

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Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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Authors: M. Hakami, A. Jammaly, I. Attafi, M. Oraiby, M. Jeraiby

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We reviewed an unusual case of a 65-year-old male taking an herbal mixture containing compounds with anticholinesterase activity for a long period of time, presented with acute my myocardial infarction and multiple organ dysfunction syndrome followed by death. Clinically, there are findings correlated with anticholinesterase activity, such as bilateral miosis, diaphoresis, vomiting and fasciculation without a history of any toxic ingestion or exposure. Gas chromatography–mass spectrometry screening studies identified the presence of thymol, anethole in the herbal extract and butylated hydroxytoluene in the blood sample. Hence, with this case report, we intend to highlight the necessity of evaluating the long-term use of the herbal mixture.

Keywords: cholinesterase inhibitors, thymole, anethole, butylatedhydroxytoluene, cardiac toxicity, myocardial infarction

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Authors: Sulemana Saibu, Moses Ikpeme

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Background: The severity of the COVID-19 pandemic, brought on by the SARS-CoV-2 coronavirus, has been unprecedented since the 1918 influenza pandemic. SARS-CoV-2 cases of CNS and peripheral nervous system disease, including neurodegenerative disorders and chronic immune-mediated diseases, may be anticipated based on knowledge of past coronaviruses, particularly those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. Although respiratory symptoms are the most common clinical presentation, neurological symptoms are becoming increasingly recognized, raising concerns about their potential role in causing Parkinson's disease, Multiple sclerosis, and Narcolepsy. This systematic review aims to summarize the current evidence by exploring the association between COVID-19 infection and how it may overlap with etiological mechanisms resulting in Narcolepsy, Parkinson's disease, and Multiple sclerosis. Methods: A systematic search was conducted using electronic databases ((PubMed/MedLine, Embase, PsycINFO, ScieLO, Web of Science, ProQuest (Biotechnology, Virology, and AIDS), Scopus, and CINAHL)) to identify studies published between January 2020 and December 2022 that investigated the association between COVID-19 and Parkinson's disease, multiple sclerosis, and Narcolepsy. Per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the review was performed and reported. Study quality was assessed using the Critical Appraisal Skills Programme Checklist and the Joanna Briggs Institute Critical appraisal tools. Results: A total of 21 studies out of 1025 met the inclusion criteria, including 8 studies reporting Parkinson's disease, 11 on multiple sclerosis, and 2 on Narcolepsy. In COVID-19 individuals compared to the general population, Narcolepsy, Parkinson's disease, and multiple sclerosis were shown to have a higher incidence. The findings imply that COVID-19 may worsen the signs or induce multiple sclerosis and Parkinson's disease and may raise the risk of developing Narcolepsy. Further research is required to confirm these connections because the available data is insufficient. Conclusion: According to the existing data, COVID-19 may raise the risk of Narcolepsy and have a causative relationship with Parkinson's disease, multiple sclerosis, and other diseases. More study is required to confirm these correlations and pinpoint probable mechanisms behind these interactions. Clinicians should be aware of how COVID-19 may affect various neurological illnesses and should treat patients who are affected accordingly.

Keywords: COVID-19, parkinson’s disease, multiple sclerosis, narcolepsy, neurological disorders, sars-cov-2, neurodegenerative disorders, chronic immune-mediated diseases

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Authors: Kazeem Adesina Dauda, Waheed Babatunde Yahya

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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

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

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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

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

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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

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Authors: Azwin Lubis, Rika Hapsari, Zahrah Hikmah, Anang Endaryanto, Ariyanto Harsono

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Erythema Multiforme Exudativum Major (EMEM) is one of the drug allergy diseases. Drug allergies caused by isoniazid rarely causes EMEM. Cutaneous reactions caused by isoniazid were obtained in 0.98% of patients, but the precise occurrence of Steven Johnson’s Syndrome (SJS) and Toxic Epidermolisis Necrolisis (TEN) due to isoniazid is not known for certain. We present this case to show hypersensitivity of isoniazid in a child. Based on the history of drug intake, physical diagnostic tests, drug elimination and provocation; we established the diagnosis of isoniazid hypersensitivity. The child showed improvement on skin manifestation after stopped isoniazid therapy.

Keywords: erythema multiforme exudativum major, hypersensitivity, elimination test, provocation test

Procedia PDF Downloads 249

Authors: Mustafa M. Donma, Orkide Donma

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The impact of metabolic syndrome (MetS) on cognition and functions of the brain is being investigated. Iron deficiency and deficiencies of B9 (folate) as well as B12 (cobalamin) vitamins are best-known nutritional anemias. They are associated with cognitive disorders and learning difficulties. The antidepressant effects of vitamin D are known and the deficiency state affects mental functions negatively. The aim of this study is to investigate possible correlations of MetS with serum brain-derived neurotrophic factor (BDNF), iron, folate, cobalamin and vitamin D in pediatric patients. 30 children, whose age- and sex-dependent body mass index (BMI) percentiles vary between 85 and 15, 60 morbid obese children with above 99^th percentiles constituted the study population. Anthropometric measurements were taken. BMI values were calculated. Age- and sex-dependent BMI percentile values were obtained using the appropriate tables prepared by the World Health Organization (WHO). Obesity classification was performed according to WHO criteria. Those with MetS were evaluated according to MetS criteria. Serum BDNF was determined by enzyme-linked immunosorbent assay. Serum folate was analyzed by an immunoassay analyzer. Serum cobalamin concentrations were measured using electrochemiluminescence immunoassay. Vitamin D status was determined by the measurement of 25-hydroxycholecalciferol [25-hydroxy vitamin D3, 25(OH)D] using high performance liquid chromatography. Statistical evaluations were performed using SPSS for Windows, version 16. The p values less than 0.05 were accepted as statistically significant. Although statistically insignificant, lower folate and cobalamin values were found in MO children compared to those observed for children with normal BMI. For iron and BDNF values, no alterations were detected among the groups. Significantly decreased vitamin D concentrations were noted in MO children with MetS in comparison with those in children with normal BMI (p ≤ 0.05). The positive correlation observed between iron and BDNF in normal-BMI group was not found in two MO groups. In THE MetS group, the partial correlation among iron, BDNF, folate, cobalamin, vitamin D controlling for waist circumference and BMI was r = -0.501; p ≤ 0.05. None was calculated in MO and normal BMI groups. In conclusion, vitamin D should also be considered during the assessment of pediatric MetS. Waist circumference and BMI should collectively be evaluated during the evaluation of MetS in children. Within this context, BDNF appears to be a key biochemical parameter during the examination of obesity degree in terms of mental functions, cognition and learning capacity. The association observed between iron and BDNF in children with normal BMI was not detected in MO groups possibly due to development of inflammation and other obesity-related pathologies. It was suggested that this finding may contribute to mental function impairments commonly observed among obese children.

Keywords: brain-derived neurotrophic factor, iron, vitamin B9, vitamin B12, vitamin D

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

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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

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Authors: Zakieh Rostamzadeh, Zahra Shirmohammadi

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Human cytomegalovirus is a species of the cytomegalovirus family of viruses, which in turn is a member of the viral family known as herpesviridae or herpesviruses. Although they may be found throughout the body, HCMV infections are frequently associated with the salivary glands. HCMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised such as HIV-infected persons, organ transplant recipients, or newborn infants. After infection, HCMV has an ability to remain latent within the body over long periods. Cytomegalovirus (CMV) causes infection in immunocompromised, hemophilia patients and those who received blood transfusion frequently. This study aimed at determining the prevalence of cytomegalovirus (CMV) antibodies in hemophilia patients. Materials and Methods: A retrospective observational study was carried out in Urmia, North West of Iran. The study population comprised a sample of 50 hemophilic patients born after 1985 and have received blood factors in West Azerbaijan. The exclusion criteria include: drug abusing, high risk sexual contacts, vertical transmission of mother to fetus and suspicious needling. All samples were evaluated with the method of ELISA, with a certain kind of kit and by a certain laboratory. Results: Fifty hemophiliacs from 250 patients registered with Urmia Hemophilia Society were enrolled in the study including 43 (86%) male, and 7 (14%) female. The mean age of patients was 10.3 years, range 3 to 25 years. None of patients had risk factors mentioned above. Among our studied population, 34(68%) had hemophilia A, 1 (2%) hemophilia B, 8 (16%) VWF, 3(6%) factor VII deficiency, 1 (2%) factor V deficiency, 1 (2%) factor X deficiency, 1 (2%). Sera of 50 Hemodialysis patients were investigated for CMV-specific immunoglobulin G (IgG) and IgM. % 91.89 patients were anti-CMV IgG positive and %40.54 was seropositive for anti-CMV IgM. 37.8% patient had serological evidence of reactivation and 2.7% of patients had the primary infection. Discussion: There was no relationship between the antibody titer and: drug abusing, high risk sexual contacts, vertical transmission of mother to fetus and suspicious needling.

Keywords: bioinformatics, biomedicine, cytomegalovirus, immunocompromise

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Authors: Elizabeth Ankiambom Chiatii

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The effective participation of graduates as leaders in entrepreneurial resilience is a key driver to achieving sustainable job creation and curbing unemployment issues in the urban and rural communities of Cameroon. The unemployment problem is a global challenge in the Labour market, especially for youths graduating from universities. Statistics from the Cameroon National Institute of statistics indicate that the unemployment rate in the country increased to 3.9% in 2021 from 3.8% in 2020. One of the main causes of unemployment challenges and job hooping among university graduates is the high expectation for “white-collar jobs syndrome” as opposed to involvement in ‘blue-collar jobs’. In the recent years, the Catholic University of Cameroon has engaged its resources in problem and project based learning (PBL) approaches in order to enable the students at the end of their course work to be competent and resourceful in impacting their communities and the world at large. It is so encouraging to notice that most of our current and female ex-students have engaged as leaders in fostering entrepreneurial resilience through small and medium size ‘blue-collar’ enterprises like seamstresses or tailors, designers, catering services, poultry owners, traditional regalia designers, phone booth operators, farming (gardening) activities, saloon owners, wedding designers, restaurant operators and many other creative jobs where they also act as petty employers. A good number of them sponsor their university studies through these self-income generating activities. Part one of this paper centres on the introduction and background of study. Part two embodies some literature review in which we concentrate on some related conceptual issues. For example, we have some analogy of employment difficulties faced by the university graduates. Secondly, we will examine the details on entrepreneurial resilience within the context of Bamenda- Cameroon. Thirdly, we expound on the leadership role played by these graduates in building resilience as entrepreneurs stemming from their university training. The primary method of data collection is implemented, where questionnaires are distributed to at least 100 of these graduates engaged in building entrepreneurial resilience. The IVProbit regression analysis is used to determine the effect of these graduate participation as leader on entrepreneurial resilience. The results can contribute to the development of entrepreneurial resilience, and recommendations will be made to CATUC Bamenda, some communities and government leaders to enhance their policies to empower these young graduates in fostering these resourceful activities.

Keywords: graduates entrepreneurial resilience, unemployment challenges, white-collar job syndrome, small and medium size blue-collar enterprises

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Authors: Laila Seada, Ashraf Ibrahim, Amjad Al Shammari

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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

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Authors: Noah Yusuf

Abstract:

The present paper examined the current level of socio-political and economic development in Africa. Models and experiences from other regions of the world, especially, developing ones with similar historical experience with Africa, were explored. The paper concluded that recommendations emanating from past conferences, seminars and symposia on the continent’s socio-economic and political challenges have been poorly implemented because of lack of strong political will; the donor syndrome; weak resource base; capacity constraints in institutions; and lack of accountability, transparency and poor governance. It is, therefore, recommended that African countries need implement sound policies and reforms on a comprehensive basis, if they are to achieve the desired socio-economic and political transformation; and the African in Diasporas represent critical instruments in attaining the socio-economic and political objectives of the continent.

Keywords: Africa, political transformation, economic transformation, Africans in diasporas

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

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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

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Authors: Razvan Mercut, Mihaela Ionescu, Vlad Parvanescu, Razvan Ghita, Tudor-Gabriel Caragea, Cristina Simionescu, Marius-Eugen Ciurea

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Introduction: Over the past years, the incidence of non-melanoma skin cancer (NMSC) has continuously increased, being one of the most commonly diagnosed carcinomasofthe cephalic extremity. NMSC regroups basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma, cutaneous lymphoma, and sarcoma. The most common forms are BCC and SCC, both still implying a significant level of morbidity due to local invasion (especially BCC), even if the overall death rates are declining. The objective of our study was the evaluation of clinical and histological aspects of NMSC for a group of patients with BCC and SCC, from Craiova, a south-western major city in Romania. Materialand method: Our study lot comprised 65 patients, with an almost equal distribution of sexes, and ages between 23-91 years old (mean value±standard deviation62.61±16.67), all treated within the Clinic of Plastic Surgery and Reconstructive Microsurgery, Clinical Emergency County Hospital Craiova, Romania, between 2019-2020. In order to determine the main morphological characteristics of both studied cancers, we used paraffin embedding techniques, with various staining methods:hematoxylin-eosin, Masson's trichrome stain with aniline blue, and Periodic acid-schiffAlcian Blue. The statistical study was completed using Microsoft Excel (Microsoft Corp., Redmond, WA, USA), with XLSTAT (Addinsoft SARL, Paris, France). Results: The overall results of our study indicate that BCC accounts for 67.69% of all NMSC forms; SCC covers 27.69%, while 4.62% are representedby other forms. The most frequent site is the nose for BCC (27.69%, 18 patients), being followed by preauricular regions, forehead, and periorbital areas. For patients with SCC, tumors were mainly located at lips level (66.67%, 12 patients). The analysis of NMSC histological forms indicated that nodular BCC is predominant (45.45%, 20 patients), as well as ulcero-vegetant SCC (38.89%, 7 patients). We have not identified any topographic characteristics or NMSC forms significantly related to age or sex. Conclusions: The most frequent NMSC form identified for our study lot was BCC. The preferred location was the nose for BCC. For SCC, the oral cavity is the most frequent anatomical site, especially the lips level. Nodular BCC and ulcero-vegetant SCC were the most commonly identified histological types. Our findings emphasize the need for periodic screening, in order to improve prevention and early treatment for these malignancies.

Keywords: non-melanoma skin cancer, basal cell carcinoma, squamous cell carcinoma, histological

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

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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

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

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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

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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

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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

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

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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

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Authors: Elena E. Lyakso, Olga V. Frolova, Yuri N. Matveev, Aleksey S. Grigorev, Alexander S. Nikolaev, Viktor A. Gorodnyi

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The study of the children’s emotional sphere depending on age and psychoneurological state is of great importance for the design of educational programs for children and their social adaptation. Atypical development may be accompanied by violations or specificities of the emotional sphere. To study characteristics of the emotional state reflection in the voice and speech features of children, the perceptual study with the participation of adults and the automatic recognition of speech were conducted. Speech of children with typical development (TD), with Down syndrome (DS), and with autism spectrum disorders (ASD) aged 6-12 years was recorded. To obtain emotional speech in children, model situations were created, including a dialogue between the child and the experimenter containing questions that can cause various emotional states in the child and playing with a standard set of toys. The questions and toys were selected, taking into account the child’s age, developmental characteristics, and speech skills. For the perceptual experiment by adults, test sequences containing speech material of 30 children: TD, DS, and ASD were created. The listeners were 100 adults (age 19.3 ± 2.3 years). The listeners were tasked with determining the children’s emotional state as “comfort – neutral – discomfort” while listening to the test material. Spectrographic analysis of speech signals was conducted. For automatic recognition of the emotional state, 6594 speech files containing speech material of children were prepared. Automatic recognition of three states, “comfort – neutral – discomfort,” was performed using automatically extracted from the set of acoustic features - the Geneva Minimalistic Acoustic Parameter Set (GeMAPS) and the extended Geneva Minimalistic Acoustic Parameter Set (eGeMAPS). The results showed that the emotional state is worse determined by the speech of TD children (comfort – 58% of correct answers, discomfort – 56%). Listeners better recognized discomfort in children with ASD and DS (78% of answers) than comfort (70% and 67%, respectively, for children with DS and ASD). The neutral state is better recognized by the speech of children with ASD (67%) than by the speech of children with DS (52%) and TD children (54%). According to the automatic recognition data using the acoustic feature set GeMAPSv01b, the accuracy of automatic recognition of emotional states for children with ASD is 0.687; children with DS – 0.725; TD children – 0.641. When using the acoustic feature set eGeMAPSv01b, the accuracy of automatic recognition of emotional states for children with ASD is 0.671; children with DS – 0.717; TD children – 0.631. The use of different models showed similar results, with better recognition of emotional states by the speech of children with DS than by the speech of children with ASD. The state of comfort is automatically determined better by the speech of TD children (precision – 0.546) and children with ASD (0.523), discomfort – children with DS (0.504). The data on the specificities of recognition by adults of the children’s emotional state by their speech may be used in recruitment for working with children with atypical development. Automatic recognition data can be used to create alternative communication systems and automatic human-computer interfaces for social-emotional learning. Acknowledgment: This work was financially supported by the Russian Science Foundation (project 18-18-00063).

Keywords: autism spectrum disorders, automatic recognition of speech, child’s emotional speech, Down syndrome, perceptual experiment

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