Search results for: radical nephrectomy with tumor thrombectomy

Authors: Rajish Shil, Amal Alduhoori, Vipin Thomachan, Jamal Teir, Radhakrishnan Renganathan

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Background: Antiphospholipid antibody syndrome (APS) has a broad spectrum of thrombotic and non-thrombotic clinical manifestations. We present a case of APS presenting with seizure, stroke, and atrial mass. Case Description: A 38-year-old male presented with headache of 10 days duration and tonic-clonic seizure. The neurological examination was normal. Magnetic resonance imaging of brain showed small acute right cerebellar infarct. Magnetic resonance angiography of brain and neck showed a focal narrowing in the origin of the internal carotid artery bilaterally. Electroencephalogram was normal. He was started on aspirin, atorvastatin, and carbamazepine. Transthoracic and trans-esophageal echocardiography showed a pedunculated and lobular atrial mass, measuring 1 X 1.5 cm, which was freely mobile across mitral valve opening across the left ventricular inflow. Autoimmune screening showed positive Antiphospholipid antibodies in high titer (Cardiolipin IgG > 120 units/ml, B2 glycoprotein IgG 90 units/mL). Anti-nuclear antibody was negative. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Platelet count was low (111 x 109/L). The patient underwent successful surgical removal of the mass, which looked like a thrombotic clot, and Histopathological analysis confirmed it as a fibrinous clot, with no evidence of tumor cells. The patient was started on full anticoagulation treatment and was followed up regularly in the clinic, where our patient did not have any further complications from the disease. Discussion: Our patient was diagnosed to have APS based on the features of high positive anticardiolipin antibody IgG and B2 glycoprotein IgG levels, Stroke, thrombocytopenia, and abnormal echo findings. Thrombotic vegetation can mimic an atrial myxoma on echo. Conclusion: APS can present with neurological and cardiac manifestations, and therefore a high index of suspicion is necessary for a diagnosis of the disease as it can affect both short and long term treatment plans and prognosis. Therefore, in patients presenting with neurological symptoms like seizures, weakness and radiological diagnosis of stroke in a young patient, where atrial masses could be thought to be the cause of stroke, they should be screened for any concomitant findings of thrombocytopenia and/or activated partial thromboplastin time prolongation, which should raise the suspicion of vasculitis, specifically APS to be the primary cause of the clinical presentation.

Keywords: antiphospholipid syndrome, seizures, atrial mass, stroke

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Authors: G. V. Manzane, S. J. Modise

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Uterine fibroids, also known as leiomyomas or myomas, are non-cancerous growths that develop in the muscular wall of the uterus during the reproductive years. The cause of uterine fibroids includes hormonal, genetic, growth factors, and extracellular matrix factors. Common symptoms of uterine fibroids include heavy and prolonged menstrual bleeding which can lead to a high risk of anemia, lower abdominal pains, pelvic pressure, infertility, and pregnancy loss. The growth of this tumor is a concern because of its negative impact on women’s health and the increase in their economic burden. Traditional medicinal plants have long been used in Africa for their potential therapeutic effects against various ailments. In this study, we aimed to identify and characterize bioactive compounds from selected African medicinal plants with potential anti-fibrotic properties using Fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GCMS) analysis. Two medicinal plant species known for their traditional use in fibrosis-related conditions were selected for investigation. Aqueous extracts were prepared from the plant materials, and FTIR analysis was conducted to determine the functional groups present in the extracts. GCMS analysis was performed to identify the chemical constituents of the extracts. The FTIR analysis revealed the presence of various functional groups, such as phenols, flavonoids, terpenoids, and alkaloids, known for their potential therapeutic activities. These functional groups are associated with antioxidant, anti-inflammatory, and anti-fibrotic properties. The GCMS analysis identified several bioactive compounds, including flavonoids, alkaloids, terpenoids, and phenolic compounds, which are known for their pharmacological activities. The discovery of bioactive compounds in African medicinal plants that exhibit anti-fibrotic effects, opens up promising avenues for further research and development of potential treatments for fibrosis. This suggests the potential of these plants as a valuable source of novel therapeutic agents for treating fibrosis-related conditions. In conclusion, our study identified and characterized bioactive compounds from selected African medicinal plants using FTIR and GCMS analysis. The presence of compounds with known antifibrotic properties suggests that these plants hold promise as a potential source of natural products for the development of novel anti-fibrotic therapies.

Keywords: uterine fibroids, african medicinal plants, bioactive compounds, identify and characterized

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

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

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

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Authors: Jeongyeon Park, Yeo Jun Yoon, Jiyoung Seo, In Seok Moon, Hae Jun Lee, Kiwon Song

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Cold Atmospheric Pressure Plasma (CAPP) is defined as a partially ionized gas with electrically charged particles at room temperature and atmospheric pressure. CAPP generates reactive oxygen species (ROS) and reactive nitrogen species (RNS), and has potential as a new apoptosis-promoting cancer therapy. With an annular type dielectric barrier discharge (DBD) CAPP-generating device combined with a helium (He) gas feeding system, we showed that CAPP selectively induced apoptosis in various cancer cells while it promoted proliferation of the adipose tissue-derived stem cell (ASC). The apoptotic effect of CAPP was highly selective toward p53-mutated cancer cells. The intracellular ROS was mainly responsible for apoptotic cell death in CAPP-treated cancer cells. CAPP induced apoptosis even in doxorubicin-resistant cancer cell lines, demonstrating the feasibility of CAPP as a potent cancer therapy. With the same device and exposure conditions to cancer cells, CAPP stimulated proliferation of the ASC, a kind of mesenchymal stem cell that is capable of self-renewing and differentiating into adipocytes, chondrocytes, osteoblasts and neurons. CAPP-treated ASCs expressed the stem cell markers and differentiated into adipocytes as untreated ASCs. The increase of proliferation by CAPP in ASCs was offset by a NO scavenger but was not affected by ROS scavengers, suggesting that NO generated by CAPP is responsible for the activated proliferation in ASCs. Usually, cancer stem cells are reported to be resistant to known cancer therapies. When we applied CAPP of the same device and exposure conditions to cancer cells to liver cancer stem cells (CSCs) that express CD133 and epithelial cell adhesion molecule (EpCAM) cancer stem cell markers, apoptotic cell death was not examined. Apoptotic cell death of liver CSCs was induced by the CAPP generated from a device with an air-based flatten type DBD. An exposure of liver CSCs to CAPP decreased the viability of liver CSCs to a great extent, suggesting plasma be used as a promising anti-cancer treatment. To validate whether CAPP can be a promising anti-cancer treatment or an adjuvant modality to eliminate remnant tumor in cancer surgery of vestibular schwannoma, we applied CAPP to mouse schwannoma cell line SC4 Nf2 ‑/‑ and human schwannoma cell line HEI-193. A CAPP treatment leads to anti-proliferative effect in both cell lines. We are currently studying the molecular mechanisms of differential physiological effect of CAPP; the proliferation of ASCs and apoptosis of various cancer cells and CSCs.

Keywords: cold atmospheric pressure plasma, apoptosis, proliferation, cancer cells, adult stem cells

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Authors: Ahmed Abdallatif

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Background: Patients with malignant germ cell tumors have age distribution in two peaks, with the first one during infancy and the second after the onset of puberty. Gonadal germ cell tumors are the most common malignant ovarian tumor in females aged below twenty years. Sacrococcygeal and retroperitoneal abdominal tumors usually presents in a large size before the onset of symptoms. Methods: Patients with pediatric germ cell tumors presenting to Children’s Cancer Hospital Egypt and National Cancer Institute Egypt from January 2008 to June 2011 Patients underwent stratification according to risk into low, intermediate and high risk groups according to children oncology group classification. Objectives: Assessment of the clinicopathologic features of all cases of pediatric germ cell tumors and classification of malignant cases according to their stage, and the primary site to low, intermediate and high risk patients. Evaluation of surgical management in each group of patients focusing on surgical approach, the extent of surgical resection according to each site, ability to achieve complete surgical resection and perioperative complications. Finally, determination of the three years overall and disease-free survival in different groups and the relation to different prognostic factors including the extent of surgical resection. Results: Out of 131 cases surgically explored only 26 cases had re exploration with 8 cases explored for residual disease 9 cases for remote recurrence or metastatic disease and the other 9 cases for other complications. Patients with low risk kept under follow up after surgery, out of those of low risk group (48 patients) only 8 patients (16.5%) shifted to intermediate risk. There were 20 patients (14.6%) diagnosed as intermediate risk received 3 cycles of compressed (Cisplatin, Etoposide and Bleomycin) and all high risk group patients 69patients (50.4%) received chemotherapy. Stage of disease was strongly and significantly related to overall survival with a poorer survival in late stages (stage IV) as compared to earlier stages. Conclusion: Overall survival rate at 3 three years was (76.7% ± 5.4, 3) years EFS was (77.8 % ±4.0), however 3 years DFS was much better (89.8 ± 3.4) in whole study group with ovarian tumors had significantly higher Overall survival (90% ± 5.1). Event Free Survival analysis showed that Male gender was 3 times likely to have bad events than females. Patients who underwent incomplete resection were 4 times more than patients with complete resection to have bad events. Disease free survival analysis showed that Patients who underwent incomplete surgery were 18.8 times liable for recurrence compared to those who underwent complete surgery, and patients who were exposed to re-excision were 21 times more prone to recurrence compared to other patients.

Keywords: extragonadal, germ cell tumors, gonadal, pediatric

Procedia PDF Downloads 207

Authors: Nonita Sarin, K.J.Singh, Anuj Kumar, Davinder Singh

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Polymeric 3D hydrogels have pivotal role in bone tissue regeneration applications. Hydrogels behave similar to the living tissues because they have large water imbibing capacity in swollen state and adjust their shape according to the tissues during tissue formation after implantation. On the other hand, hydrogels are very soft, fragile and lack mechanical strength. Incorporation of bioceramics can improve mechanical strength. Furthermore, bioceramics synthesized by sol gel technique may enhance the apatite formation and degradation rates which can lead to the increase in faster rates for new bone and tissue regeneration. Simulated body fluid (SBF) induces the poly-condensation of silanol groups which leads to formation of silica matrix and provide active sites for the precipitation of Ca2+ and PO43- ions to form apatite layer which is similar to mineral form of bone. Therefore, authors have synthesized bioceramic incorporated Polyacrylamide-carboxymethylcellulose hydrogels by free radical polymerization and bioceramic compositions of xSrO-(36-x)CaO-45SiO2-ySeO3-(12-y)P2O5-7MgO (where x=0,4 and y=0,2 mol%) were synthesized by sol gel technique. Bioceramics incorporated in polymer matrix induces quicker apatite formation during immersion in SBF by raising the pH with the release of alkaline ions during ion exchange process and the apatite formation takes place in alkaline medium. The behavior of samples PABC-0 (without bioceramics) and PABC-20 (with 20 wt% bioceramics) were evaluated by X-Ray Diffraction and FTIR. In term of bioactivity, it was observed that PABC-20 has shown hydroxyapatite (HA) formation on 1st day of immersion whereas, PABC-0 was shown apatite formation on 7th day of immersion in SBF. The rapid rate of HA growth on 1st day of immersion in SBF signifies easy regeneration of damaged bone tissues. Degradation studies have been undertaken in Phosphate Buffer Saline and PABC-20 exhibited slower degradation rate up to 9%as compared to PABC-0 up to 18%. Slower degradation rate is suitable for new tissue regeneration and cell attachment. Also, Zeta potential studies have been employed to check the surface charge and it has been observed that samples carry negative charge when immersed in SBF. In addition, the swelling test of the samples have been performed and relative swelling ratio % observed for PABC-0 is 607% and PABC-20 is 305%. This indicates that the incorporation of bioceramics leads to the filling up of the voids in between the polymer matrix which in result reduces porosity and increase the mechanical strength by filling the voids. The porosity of PABC-0 is 84% and PABC-20 is 72%. PABC-20 sample demonstrates that bioceramics incorporation reduce the porosity and improves mechanical strength. Also, maximum in vitro cell viability up to 98% with MG63 cell line has been observed which indicate that the bioceramic incorporated hydrogel(PABC-20) provide the alkaline medium which is suitable environment for cell growth.

Keywords: hydrogels, hydroxyapatite, MG63 cell line, zeta potential

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Sean Griffiths

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Introduction: This paper examines the expression of ‘objectivity’ in architecture in the context of the post-war rejection of this concept. It aims to re-examine the question in light of the assault on truth characterizing contemporary culture and of the unassailable truth of the climate emergency. The paper analyses the search for objective truth as it was prosecuted in the Modern Movement in the early 20th century, looking at the extent to which this quest was successful in contributing to the development of a radically new, politically-informed architecture and the extent to which its particular interpretation of objectivity, limited that development. The paper studies the influence of the Vienna Circle philosophers Rudolph Carnap and Otto Neurath on the pedagogy of the Bauhaus and the architecture of the Neue Sachlichkeit in Germany. Their logical positivism sought to determine objective truths through empirical analysis, expressed in an austere formal language as part of a ‘scientific world conception’ which would overcome metaphysics and unverifiable mystification. These ideas, and the concurrent prioritizing of measurement as the determinant of environmental quality, became key influences in the socially-driven architecture constructed in the 1920s and 30s by Bauhaus architects in numerous German Cities. Methodology: The paper reviews the history of the early Modern Movement and summarizes accounts of the relationship between the Vienna Circle and the Bauhaus. It looks at key differences in the approaches Neurath and Carnap took to the achievement of their shared philosophical and political aims. It analyses how the adoption of Carnap’s foundationalism influenced the architectural language of modern architecture and compares, through a close reading of the structure of Neurath’s ‘protocol sentences,’ the latter’s alternative approach, speculating on the possibility that its adoption offered a different direction of travel for Modern Architecture. Findings: The paper finds that the adoption of Carnap’s foundationalism, while helping Modern Architecture forge a new visual language, ultimately limited its development and is implicated in its failure to escape the very metaphysics against which it had set itself. It speculates that Neurath’s relational language-based approach to the issue of establishing objectivity has its architectural corollary in the process of revision and renovation that offers new ways an ‘objective’ language of architecture might be developed in a manner that is more responsive to our present-day crisis. Conclusion: The philosophical principles of the Vienna Circle and the architects of the Modern Movement had much in common. Both contributed to radical historical departures which sought to instantiate a world scientific conception in their respective fields, which would attempt to banish mystification and metaphysics and would align itself with socialism. However, in adopting Carnap’s foundationalism as the theoretical basis for the new architecture, Modern Architecture not only failed to escape metaphysics but arguably closed off new avenues of development to itself. The adoption of Neurath’s more open-ended and interactive approach to objectivity offers possibilities for new conceptions of the expression of objectivity in architecture that might be more tailored to the multiple crises we face today.

Keywords: Bauhaus, logical positivism, Neue Sachlichkeit, rationalism, Vienna Circle

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Authors: Martyna Chotomska, Aleksandra Studzinska, Marta Lisowska, Justyna Szubert, Aleksandra Tabis, Jacek Bania, Arkadiusz Miazek

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Objectives: Assessing antigen-specific T cell responses is of utmost importance for the pre-clinical testing of prototype vaccines against intracellular pathogens and tumor antigens. Mainly two types of in vitro assays are used for this purpose 1) enzyme-linked immunospot (ELISpot) and 2) intracellular cytokine staining (ICS). Both are time-consuming, relatively expensive, and require manual dexterity. Here, we assess if a straightforward detection of luciferase activity in blood samples of transgenic reporter mice expressing a secreted Lucia luciferase under the transcriptional control of IFN-γ promoter parallels the sensitivity of IFNγ ELISpot assay. Methods: IFN-γ-LUCIA mouse strain carrying multiple copies of Lucia luciferase transgene under the transcriptional control of IFNγ minimal promoter were generated by pronuclear injection of linear DNA. The specificity of transgene expression and mobilization was assessed in vitro using transgenic splenocytes exposed to various mitogens. The IFN-γ-LUCIA mice were immunized with 50mg of ovalbumin (OVA) emulsified in incomplete Freund’s adjuvant three times every two weeks by subcutaneous injections. Blood samples were collected before and five days after each immunization. Luciferase activity was assessed in blood serum. Peripheral blood mononuclear cells were separated and assessed for frequencies of OVA-specific IFNγ-secreting T cells. Results: We show that in vitro cultured splenocytes of IFN-γ-LUCIA mice respond by 2 and 3 fold increase in secreted luciferase activity to T cell mitogens concanavalin A and phorbol myristate acetate, respectively but fail to respond to B cell-stimulating E.coli lipopolysaccharide. Immunization of IFN-γ-LUCIA mice with OVA leads to over 4 fold increase in luciferase activity in blood serum five days post-immunization with a barely detectable increase in OVA-specific, IFNγ-secreting T cells by ELISpot. Second and third immunizations, further increase the luciferase activity and coincidently also increase the frequencies of OVA-specific T cells by ELISpot. Conclusions: We conclude that minimally invasive monitoring of luciferase secretions in blood serum of IFN-γ-LUCIA mice constitutes a sensitive method for evaluating primary and memory Th1 responses to protein antigens. As such, this method may complement existing methods for rapid immunogenicity assessment of prototype vaccines.

Keywords: ELISpot, immunogenicity, interferon-gamma, reporter mice, vaccines

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Authors: Sahar Heidary

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Radiography and radiotherapy have emerged as crucial pillars of modern medical practice, revolutionizing diagnostics and treatment for a myriad of health conditions. This abstract highlights the pivotal role of radiography and radiotherapy in favor of healthcare and society. Radiography, a non-invasive imaging technique, has significantly advanced medical diagnostics by enabling the visualization of internal structures and abnormalities within the human body. With the advent of digital radiography, clinicians can obtain high-resolution images promptly, leading to faster diagnoses and informed treatment decisions. Radiography plays a pivotal role in detecting fractures, tumors, infections, and various other conditions, allowing for timely interventions and improved patient outcomes. Moreover, its widespread accessibility and cost-effectiveness make it an indispensable tool in healthcare settings worldwide. On the other hand, radiotherapy, a branch of medical science that utilizes high-energy radiation, has become an integral component of cancer treatment and management. By precisely targeting and damaging cancerous cells, radiotherapy offers a potent strategy to control tumor growth and, in many cases, leads to cancer eradication. Additionally, radiotherapy is often used in combination with surgery and chemotherapy, providing a multifaceted approach to combat cancer comprehensively. The continuous advancements in radiotherapy techniques, such as intensity-modulated radiotherapy and stereotactic radiosurgery, have further improved treatment precision while minimizing damage to surrounding healthy tissues. Furthermore, radiography and radiotherapy have demonstrated their worth beyond oncology. Radiography is instrumental in guiding various medical procedures, including catheter placement, joint injections, and dental evaluations, reducing complications and enhancing procedural accuracy. On the other hand, radiotherapy finds applications in non-cancerous conditions like benign tumors, vascular malformations, and certain neurological disorders, offering therapeutic options for patients who may not benefit from traditional surgical interventions. In conclusion, radiography and radiotherapy stand as indispensable tools in modern medicine, driving transformative improvements in patient care and treatment outcomes. Their ability to diagnose, treat, and manage a wide array of medical conditions underscores their favor in medical practice. As technology continues to advance, radiography and radiotherapy will undoubtedly play an ever more significant role in shaping the future of healthcare, ultimately saving lives and enhancing the quality of life for countless individuals worldwide.

Keywords: radiology, radiotherapy, medical imaging, cancer treatment

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Authors: Lijuan Li

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Nitric oxide (NO) has become a fascinating entity in biological chemistry over the past few years. It is a gaseous lipophilic radical molecule that plays important roles in several physiological and pathophysiological processes in mammals, including activating the immune response, serving as a neurotransmitter, regulating the cardiovascular system, and acting as an endothelium-derived relaxing factor. NO functions in eukaryotes both as a signal molecule at nanomolar concentrations and as a cytotoxic agent at micromolar concentrations. The latter arises from the ability of NO to react readily with a variety of cellular targets leading to thiol S-nitrosation, amino acid N-nitrosation, and nitrosative DNA damage. Nitric oxide can readily bind to metals to give metal-nitrosyl (M-NO) complexes. Some of these species are known to play roles in biological NO storage and transport. These complexes have different biological, photochemical, or spectroscopic properties due to distinctive structural features. These recent discoveries have spawned a great interest in the development of transition metal complexes containing NO, particularly its iron complexes that are central to the role of nitric oxide in the body. Spectroscopic evidence would appear to implicate species of “Fe(NO)2+” type in a variety of processes ranging from polymerization, carcinogenesis, to nitric oxide stores. Our research focuses on isolation and structural studies of non-heme iron nitrosyls that mimic biologically active compounds and can potentially be used for anticancer drug therapy. We have shown that reactions between Fe(NO)2(CO)2 and a series of imidazoles generated new non-heme iron nitrosyls of the form Fe(NO)2(L)2 [L = imidazole, 1-methylimidazole, 4-methylimidazole, benzimidazole, 5,6-dimethylbenzimidazole, and L-histidine] and a tetrameric cluster of [Fe(NO)2(L)]4 (L=Im, 4-MeIm, BzIm, and Me2BzIm), resulted from the interactions of Fe(NO)2 with a series of substituted imidazoles was prepared. Recently, a series of sulfur bridged iron di nitrosyl complexes with the general formula of [Fe(µ-RS)(NO)2]2 (R = n-Pr, t-Bu, 6-methyl-2-pyridyl, and 4,6-dimethyl-2-pyrimidyl), were synthesized by the reaction of Fe(NO)2(CO)2 with thiols or thiolates. Their structures and properties were studied by IR, UV-vis, 1H-NMR, EPR, electrochemistry, X-ray diffraction analysis and DFT calculations. IR spectra of these complexes display one weak and two strong NO stretching frequencies (νNO) in solution, but only two strong νNO in solid. DFT calculations suggest that two spatial isomers of these complexes bear 3 Kcal energy difference in solution. The paramagnetic complexes [Fe2(µ-RS)2(NO)4]-, have also been investigated by EPR spectroscopy. Interestingly, the EPR spectra of complexes exhibit an isotropic signal of g = 1.998 - 2.004 without hyperfine splitting. The observations are consistent with the results of calculations, which reveal that the unpaired electron dominantly delocalize over the two sulfur and two iron atoms. The difference of the g values between the reduced form of iron-sulfur clusters and the typical monomeric di nitrosyl iron complexes is explained, for the first time, by of the difference in unpaired electron distributions between the two types of complexes, which provides the theoretical basis for the use of g value as a spectroscopic tool to differentiate these biologically active complexes.

Keywords: di nitrosyl iron complex, metal nitrosyl, non-heme iron, nitric oxide

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Authors: Christina Drosou, Konstantina E. Kyriakopoulou, Andreas Bimpilas, Dimitrios Tsimogiannis, Magdalini C. Krokida

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Rationale: Agiorgitiko is one of the most widely-grown and commercially well-established red wine varieties in Greece. Each year viticulture industry produces a large amount of waste consisting of grape skins and seeds (pomace) during a short period. Grapes contain polyphenolic compounds which are partially transferred to wine during winemaking. Therefore, winery wastes could be an alternative cheap source for obtaining such compounds with important antioxidant activity. Specifically, red grape waste contains anthocyanins and flavonols which are characterized by multiple biological activities, including cardioprotective, anti-inflammatory, anti-carcinogenic, antiviral and antibacterial properties attributed mainly to their antioxidant activity. Ultrasound assisted extraction (UAE) is considered an effective way to recover phenolic compounds, since it combines the advantage of mechanical effect with low temperature. Moreover, green solvents can be used in order to recover extracts intended for used in the food and nutraceutical industry. Apart from the extraction, pre-treatment process like drying can play an important role on the preservation of the grape pomace and the enhancement of its antioxidant capacity. Objective: The aim of this study is to recover natural extracts from winery waste with high antioxidant capacity using green solvents so they can be exploited and utilized as enhancers in food or nutraceuticals. Methods: Agiorgitiko grape pomace was dehydrated by air drying (AD) and accelerated solar drying (ASD) in order to explore the effect of the pre-treatment on the recovery of bioactive compounds. UAE was applied in untreated and dried samples using water and water: ethanol (1:1) as solvents. The total antioxidant potential and phenolic content of the extracts was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and Folin-Ciocalteu method, respectively. Finally, the profile of anthocyanins and flavonols was specified using HPLC-DAD analysis. The efficiency of processes was determined in terms of extraction yield, antioxidant activity, phenolic content and the anthocyanins and flavovols profile. Results & Discussion: The experiments indicated that the pre-treatment was essential for the recovery of highly nutritious compounds from the pomace as long as the extracts samples showed higher phenolic content and antioxidant capacity. Water: ethanol (1:1) was considered a more effective solvent on the recovery of phenolic compounds. Moreover, ASD grape pomace extracted with the solvent system exhibited the highest antioxidant activity (IC50=0.36±0.01mg/mL) and phenolic content (TPC=172.68±0.01mgGAE/g dry extract), followed by AD and untreated pomace. The major compounds recovered were malvidin3-O-glucoside and quercetin3-O-glucoside according to the HPLC analysis. Conclusions: Winery waste can be exploited for the recovery of nutritious compounds using green solvents such as water or ethanol. The pretreatment of the pomace can significantly affect the concentration of phenolic compounds, while UAE is considered a highly effective extraction process.

Keywords: agiorgitico grape pomace, antioxidants, phenolic compounds, ultrasound assisted extraction

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Authors: Alberto Veses, Olga Sanhauja, María Soledad Callén, Tomás García

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The appropriate use of renewable sources emerges as a decisive point to minimize the environmental impact caused by fossil fuels use. Particularly, the use of lignocellulosic biomass becomes one of the best promising alternatives since it is the only carbon-containing renewable source that can produce bioproducts similar to fossil fuels and it does not compete with food market. Among all the processes that can valorize lignocellulosic biomass, pyrolysis is an attractive alternative because it is the only thermochemical process that can produce a liquid biofuel (bio-oil) in a simple way and solid and gas fractions that can be used as energy sources to support the process. However, in order to incorporate bio-oils in current infrastructures and further process in future biorefineries, their quality needs to be improved. Introducing different low-cost catalysts and/or incorporating different polymer residues to the process are some of the new, simple and low-cost strategies that allow the user to directly obtain advanced bio-oils to be used in future biorefineries in an economic way. In this manner, from previous thermogravimetric analyses, local agricultural wastes such as grape seeds (GS) were selected as lignocellulosic biomass while, waste tires (WT) were selected as polymer residue. On the other hand, CaO was selected as low-cost catalyst based on previous experiences by the group. To reach this aim, a specially-designed fixed bed reactor using N₂ as a carrier gas was used. This reactor has the peculiarity to incorporate a vertical mobile liner that allows the user to introduce the feedstock in the oven once the selected temperature (550 ºC) is reached, ensuring higher heating rates needed for the process. Obtaining a well-defined phase distribution in the resulting bio-oil is crucial to ensure the viability to the process. Thus, once experiments were carried out, not only a well-defined two layers was observed introducing several mixtures (reaching values up to 40 wt.% of WT) but also, an upgraded organic phase, which is the one considered to be processed in further biorefineries. Radical interactions between GS and WT released during the pyrolysis process and dehydration reactions enhanced by CaO can promote the formation of better-quality bio-oils. The latter was reflected in a reduction of water and oxygen content of bio-oil and hence, a substantial increase of its heating value and its stability. Moreover, not only sulphur content was reduced from solely WT pyrolysis but also potential and negative issues related to a strong acidic environment of conventional bio-oils were minimized due to its basic pH and lower total acid numbers. Therefore, acidic compounds obtained in the pyrolysis such as CO₂-like substances can react with the CaO and minimize acidic problems related to lignocellulosic bio-oils. Moreover, this CO₂ capture promotes H₂ production from water gas shift reaction favoring hydrogen-transfer reactions, improving the final quality of the bio-oil. These results show the great potential of grapes seeds to carry out the catalytic co-pyrolysis process with different plastic residues in order to produce a liquid bio-oil that can be considered as a high-quality renewable vector.

Keywords: advanced bio-oils, biorefinery, catalytic co-pyrolysis of biomass and waste tires, lignocellulosic biomass

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Authors: Fatemeh Sadeghi, Peyman Sheikhzadeh

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Introduction: Block Sequential Regularized Expectation Maximization (BSREM) reconstruction algorithm was recently developed to suppress excessive noise by applying a relative difference penalty. The aim of this study was to investigate the effect of various strengths of noise penalization factor in the BSREM algorithm under different acquisition duration and lesion sizes in order to determine an optimum penalty factor by considering both quantitative and qualitative image evaluation parameters in clinical uses. Materials and Methods: The NEMA IQ phantom and 15 clinical whole-body patients with prostate cancer were evaluated. Phantom and patients were injected withGallium-68 Prostate-Specific Membrane Antigen(68 Ga-PSMA)and scanned on a non-time-of-flight Discovery IQ Positron Emission Tomography/Computed Tomography(PET/CT) scanner with BGO crystals. The data were reconstructed using BSREM with a β-value of 100-500 at an interval of 100. These reconstructions were compared to OSEM as a widely used reconstruction algorithm. Following the standard NEMA measurement procedure, background variability (BV), recovery coefficient (RC), contrast recovery (CR) and residual lung error (LE) from phantom data and signal-to-noise ratio (SNR), signal-to-background ratio (SBR) and tumor SUV from clinical data were measured. Qualitative features of clinical images visually were ranked by one nuclear medicine expert. Results: The β-value acts as a noise suppression factor, so BSREM showed a decreasing image noise with an increasing β-value. BSREM, with a β-value of 400 at a decreased acquisition duration (2 min/ bp), made an approximately equal noise level with OSEM at an increased acquisition duration (5 min/ bp). For the β-value of 400 at 2 min/bp duration, SNR increased by 43.7%, and LE decreased by 62%, compared with OSEM at a 5 min/bp duration. In both phantom and clinical data, an increase in the β-value is translated into a decrease in SUV. The lowest level of SUV and noise were reached with the highest β-value (β=500), resulting in the highest SNR and lowest SBR due to the greater noise reduction than SUV reduction at the highest β-value. In compression of BSREM with different β-values, the relative difference in the quantitative parameters was generally larger for smaller lesions. As the β-value decreased from 500 to 100, the increase in CR was 160.2% for the smallest sphere (10mm) and 12.6% for the largest sphere (37mm), and the trend was similar for SNR (-58.4% and -20.5%, respectively). BSREM visually was ranked more than OSEM in all Qualitative features. Conclusions: The BSREM algorithm using more iteration numbers leads to more quantitative accuracy without excessive noise, which translates into higher overall image quality and lesion detectability. This improvement can be used to shorter acquisition time.

Keywords: BSREM reconstruction, PET/CT imaging, noise penalization, quantification accuracy

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Authors: Rosemary R. Carlton, Roxane Caron

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Almost three decades ago, bell hooks (1994) identified the classroom as “the most radical space of possibility in the academy”. A feminist scholar, educator, and activist, hooks urged educators to transgress the boundaries of what might be customary or considered acceptable in teaching, thus encouraging the pursuit of new ways of knowing and different strategies for sharing knowledge. This paper reflects upon a particular response to hooks’ still relevant call for transgression in teaching. Specifically, this paper reports on the design, implementation, and preliminary analysis of a social work course integrating active pedagogy and transnational exchange to encourage students’ critical thinking and autonomous learning in their development as social workers in a global context. The bachelor’s level course, Pratiques spécifiques: Projet international, was developed collaboratively across three francophone institutions of higher learning in Belgium, Canada, and France: the Haute École de Namur-Liège-Luxembourg (Hénallux); the Université de Montréal; and, the Institut d’enseignement supérieur et professionnel, l’IRTS Paris Île-de-France. The driving aims of the course are to promote autonomous learning and critical thinking through a lens of transnational understandings of social problems -competencies indispensable to students’ development as social workers. The course is offered to two paired cohorts, one addressing the subject of “migrations” (Canada/France) and the other the subject of “sexual exploitation” (Canada/Belgium). Through the adaptation of a critical pedagogy of problem-based learning, students are called upon to actively engage in acquiring and applying knowledge to respond to “real life” social issues relating to migration or sexual exploitation. At the conclusion of the course, each cohort of students is brought together for a week-long intensive period of transnational exchange either at the Université de Montréal in Canada or at Hénallux in Belgium. Extending the bounds of the classroom across international borders allows students novel opportunities to deepen and expand their understandings of issues relating to predefined social issues and to critically examine associated social work practices. The paper opens with a presentation of the social work course. Specifically, the authors will outline their adaptation of a pedagogy of problem-based learning integrating transnational exchange in the design and implementation of the course. Returning to hooks’ notion of transgression in teaching, the paper offers a preliminary analysis of how and with what effect the course provides opportunities to transgress hierarchical student-teacher relationships; transgress conventional modes of learning to explore diverse sources of knowledge and transgress the walls of the university to engage with and learn from local and global partners. The paper concludes with a consideration of the potential influence of such transgressions in teaching for students’ development of critical thinking in their practice of social work in global context.

Keywords: active learning, critical pedagogy, social work intervention, transnational learning

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Authors: Neha P. Amin, Maliha Zainib, Sean Parker, Malcolm Mattes

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Purpose/Objectives: Combination immunotherapy (IT) and radiation therapy (RT) is an actively growing field of clinical investigation due to promising findings of synergistic effects from immune-mediated mechanisms observed in preclinical studies and clinical data from case reports of abscopal effects. While there are many ongoing trials of combined IT-RT, there are still limited data on toxicity and outcome optimization regarding RT dose, fractionation, and sequencing of RT with IT. Nivolumab (NIVO), an anti-PD-1 monoclonal antibody, has been rapidly adopted in the clinic over the past 2 years, resulting in more patients being considered for concurrent RT-NIVO. Knowledge about the toxicity profile of combined RT-NIVO is important for both the patient and physician when making educated treatment decisions. The acute toxicity profile of concurrent RT-NIVO was analyzed in this study. Materials/Methods: A retrospective review of all consecutive patients who received NIVO from 1/2015 to 5/2017 at 4 separate centers within two separate institutions was performed. Those patients who completed a course of RT from 1 day prior to initial NIVO infusion through 1 month after last NIVO infusion were considered to have received concurrent therapy and included in the subsequent analysis. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed acute toxicities within 3 months of RT completion. Results: Among 261 patients who received NIVO, 46 (17.6%) received concurrent RT to 67 different sites. The median f/u was 3.3 (.1-19.8) months, and 11/46 (24%) were still alive at last analysis. The most common histology, RT prescription, and treatment site included non-small cell lung cancer (23/46, 50%), 30 Gy in 10 fractions (16/67, 24%), and central thorax/abdomen (26/67, 39%), respectively. 79% (53/67) of irradiated sites were treated with 3D-conformal technique and palliative dose-fractionation. Grade 3, 4, and 5 toxicities were experienced by 11, 1, and 2 patients, respectively. However all grade 4 and 5 toxicities were outside of the irradiated area and attributed to the NIVO alone, and only 4/11 (36%) of the grade 3 toxicities were attributed to the RT-NIVO. The irradiated site in these cases included the brain [2/10 (20%)] and central thorax/abdomen [2/19 (10.5%)], including one unexpected grade 3 pancreatitides following stereotactic body RT to the left adrenal gland. Conclusions: Concurrent RT-NIVO is generally well tolerated, though with potentially increased rates of severe toxicity when irradiating the lung, abdomen, or brain. Pending more definitive data, we recommend counseling patients on the potentially increased rates of side effects from combined immunotherapy and radiotherapy to these locations. Future prospective trials assessing fractionation and sequencing of RT with IT will help inform combined therapy recommendations.

Keywords: combined immunotherapy and radiation, immunotherapy, Nivolumab, toxicity of concurrent immunotherapy and radiation

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Authors: José Antonio Donaire Benito, Konstantina Zerva

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Historically, cities have been places where people from many nations and cultures have met and settled together, while population flows and density have had a significant impact on urban dynamics. Cities' high density of social, cultural, business offerings, everyday services, and other amenities not intended for tourists draw not only tourists but a wide range of city users as well. With the coordination of city rhythms and the porosity of the community, city users order and frame their urban experience. From one side, recent literature focuses on the shift in urban tourist experience from 'having' a holiday through 'doing' activities to 'becoming' a local by experiencing a part of daily life. On the other hand, there is a debate on the 'touristification of everyday life', where middle and upper class urban dwellers display attitudes and behaviors that are virtually undistinguishable from those of visitors. With the advent of globalization and technological advances, modern society has undergone a radical transformation that has altered mobility patterns within it, blurring the boundaries between tourism and everyday life, work and leisure, and "hosts" and "guests". Additionally, the presence of other 'temporary city' users, such as commuters, digital nomads, second home owners, and migrants, contributes to a more complex transformation of tourist cities. Moving away from this traditional clear distinction between 'hosts' and 'guests', which represents a more static view of tourism, and moving towards a more liquid narrative of mobility, academics on tourism development are embracing the New Mobilities Paradigm. The latter moves beyond the static structures of the modern world and focuses on the ways in which social entities are made up of people, machines, information, and images in a moving system. In light of this fluid interdependence between tourists and guests, a question arises as to whether overtourism, which is considered as the underlying cause of citizens' perception of a lower urban quality of life, is a fair representation of perceived mobility excessiveness, place consumption disruptiveness, and residents displacement. As a representative example of an overtourism narrative, Barcelona was chosen as a study area for this purpose, focusing on the incoming city users to reflect in depth the variety of people who contribute to mobility flows beyond those residents already have. Several statistical data have been analyzed to determine the number of national and international visitors to Barcelona at some point during the day in 2019. Specifically, tracking data gathered from mobile phone users within the city are combined with tourist surveys, urban mobility data, zenithal data capture, and information about the city's attractions. The paper shows that tourists are only a small part of the different incoming city users that daily enter Barcelona; excursionists, commuters, and metropolitans also contribute to a high mobility flow. Based on the diversity of incoming city users and their place consumption, it seems that the city's urban experience is more likely to be impacted by over-mobility tan over-tourism.

Keywords: city users, density, new mobilities paradigm, over-tourism.

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Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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Authors: Lesly Y Carmona-Sarabia, Luisa Barraza-Vergara, Vilmalí López-Mejías, Wandaliz Torres-García, Maribella Domenech-Garcia, Madeline Torres-Lugo

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Biosensors are used in many applications providing real-time monitoring to treat long-term conditions. Thus, understanding the physicochemical properties and biological side effects on the skin of polymers (e. g., poly(methyl methacrylate), PMMA) employed in the fabrication of wearable biosensors is crucial for the selection of manufacturing materials within this field. The PMMA (hydrophobic and thermoplastic polymer) is commonly employed as a coating material or substrate in the fabrication of wearable devices. The cytotoxicityof PMMA (including residual monomers or degradation products) on the skin, in terms of cells and tissue, is required to prevent possible adverse effects (cell death, skin reactions, sensitization) on human health. Within this work, accelerated aging of PMMA (Mw ~ 15000) through thermal and photochemical degradation was under-taken. The accelerated aging of PMMA was carried out by thermal (200°C, 1h) and photochemical degradation (UV-Vis, 8-15d) adapted employing ISO protocols (ISO-10993-12, ISO-4892-1:2016, ISO-877-1:2009, ISO-188: 2011). In addition, in vitro cytotoxicity evaluation of PMMA degradation products was performed using NIH3T3 fibroblast cells to assess the response of skin tissues (in terms of cell viability) exposed with polymers utilized to manufacture wearable biosensors, such as PMMA. The PMMA (Mw ~ 15000) before and after accelerated aging experiments was characterized by thermal gravimetric analysis (TGA), differential scanning calorimetric (DSC), powder X-ray diffractogram (PXRD), and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) to determine and verify the successful degradation of this polymer under the specific conditions previously mention. The degradation products were characterized through nuclear magnetic resonance (NMR) to identify possible byproducts generated after the accelerated aging. Results demonstrated a percentage (%) weight loss between 1.5-2.2% (TGA thermographs) for PMMA after accelerated aging. The EDS elemental analysis reveals a 1.32 wt.% loss of carbon for PMMA after thermal degradation. These results might be associated with the amount (%) of PMMA degrade after the accelerated aging experiments. Furthermore, from the thermal degradation products was detected the presence of the monomer and methyl formate (low concentrations) and a low molecular weight radical (·COOCH3) in higher concentrations by NMR. In the photodegradation products, methyl formate was detected in higher concentrations. These results agree with the proposed thermal or photochemical degradation mechanisms found in the literature.1,2 Finally, significant cytotoxicity on the NIH3T3 cells was obtained for the thermal and photochemical degradation products. A decrease in cell viability by > 90% (stock solutions) was observed. It is proposed that the presence of byproducts (e.g. methyl formate or radicals such as ·COOCH₃) from the PMMA degradation might be responsible for the cytotoxicity observed in the NIH3T3 fibroblast cells. Additionally, experiments using skin models will be employed to compare with the NIH3T3 fibroblast cells model.

Keywords: biosensors, polymer, skin irritation, degradation products, cell viability

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Authors: Peter J. Fusco, Dave M. Mathew, Chris Mathew, Kenneth H. Levy, Kathryn S. Varghese, Stephanie Salazar-Restrepo, Serena M. Mathew, Sofia Khaja, Eamon Vega, Mia Polizzi, Alyssa Mullane, Adham Ahmed

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Background: Laparoscopic (LS) removal of neuroblastomas in children has been reported to offer favorable outcomes compared to the conventional open thoracotomy (OT) procedure. Critical perioperative measures such as blood loss, operative time, length of stay, and time to postoperative chemotherapy have all supported laparoscopic use rather than its more invasive counterpart. Herein, a pairwise meta-analysis was performed comparing perioperative outcomes between LS and OT in thoracoabdominal neuroblastoma cases. Methods: A comprehensive literature search was performed on PubMed, Ovid EMBASE, and Scopus databases to identify studies comparing the outcomes of pediatric patients with thoracoabdominal neuroblastomas undergoing resection via OT or LS. After deduplication, 4,227 studies were identified and subjected to initial title screening with exclusion and inclusion criteria to ensure relevance. When studies contained overlapping cohorts, only the larger series were included. Primary outcomes include estimated blood loss (EBL), hospital length of stay (LOS), and mortality, while secondary outcomes were tumor recurrence, post-operative complications, and operation length. The “meta” and “metafor” packages were used in R, version 4.0.2, to pool risk ratios (RR) or standardized mean differences (SMD) in addition to their 95% confidence intervals in the random effects model via the Mantel-Haenszel method. Heterogeneity between studies was assessed using the I² test, while publication bias was assessed via funnel plot. Results: The pooled analysis included 209 patients from 5 studies (141 OT, 68 LS). Of the included studies, 2 originated from the United States, 1 from Toronto, 1 from China, and 1was from a Japanese center. Mean age between study cohorts ranged from 2.4 to 5.3 years old, with female patients occupying between 30.8% to 50% of the study populations. No statistically significant difference was found between the two groups for LOS (SMD -1.02; p=0.083), mortality (RR 0.30; p=0.251), recurrence(RR 0.31; p=0.162), post-operative complications (RR 0.73; p=0.732), or operation length (SMD -0.07; p=0.648). Of note, LS appeared to be protective in the analysis for EBL, although it did not reach statistical significance (SMD -0.4174; p= 0.051). Conclusion: Despite promising literature assessing LS removal of pediatric neuroblastomas, results showed it was non-superior to OT for any explored perioperative outcomes. Given the limited comparative data on the subject, it is evident that randomized trials are necessary to further the efficacy of the conclusions reached.

Keywords: laparoscopy, neuroblastoma, thoracoabdominal, thoracotomy

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Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

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Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

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Authors: Aathira Peedikaparambil Somasundaran

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The beginning of the 20th century marked the perios when a new generation of Lebanese radicals sowed the seeds for the second phase of Levant literary modernism, situated in the Levant. Beirut, during this era popularly fit every radical writer’s criterion owing to its weakened censorship and political control, despite the absence of a protective womb for the development of literary modernism, caused by the natively prevalent political unsettlement. The third stage of literary modernization, in which scholars used Western-inspired critical techniques to better understand their own cultures, coincides with the time period examined in this paper, which involved the international-inspired critical analysis of native cultural stimulants, which raised questions among Arab freethinking intellectuals. Locals who ventured outside recognised the difference between the West's progress and their own nations' stagnation. The awareness of such ‘gap of success’ aroused an ambition from journalists, authors, and proletarian revolutionaries who had studied in Europe, and finally developed enlightened ideas. Some Middle Eastern authors and artists only adopted current social and political frameworks after discovering western modernity. After learning about the upheavals that were happening in the West, these thinkers aspired to bring about equally broad drastic developments in their own country's social, political, and cultural milieu. These occurrences illustrate the increased power of migration to alter the cultural and literary scene in the Levant. The paper intends to discuss the different effects of migration that contributed to Levant literary modernism. The exploration of these factors as causes begins with addressing the politically influenced activism, that has always been a relevant part of Beirut, and then diving into the psychological effects of migration in the individuals of the society, which might have induced an accommodability to alien thoughts and ideas over time, as a coping mechanism. Nature or environmental stimuli, a common trigger for any creative output, often having the highest influence during travel will be identified and analysed to inspect the extent of its impact on the exchange of ideas that resulted in Levant modernism. The efficiency of both the stimulating component of travel and the diaspora of the indigenous, a by-product of travel in catalysing modernism in the Levant has to be proven in order to understand how migration indirectly affected the transmission and adoption of ideas in Levant literature. The paper will revisit the events revolving around these key players and platforms like Shir, to understand how the Lebanese literature, tied down in poetry drastically mutated under the leadership of Adonis, Yusuf et Khal, and other pioneers of Levant literary modernism. The conclision will identify the triggers that helped authors overcome personal and geographical barriers to unite the West and the Levant, and investigate the extent to which the bi-directional migration prompted a transformation in the local poetry. Consequently, the paper aims to shed light into the unique factor that provoked the shift in the literary scene of Twentieth century in the Middle East.

Keywords: literature, modernism, Middle East, levant, Beirut

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Authors: Fatima Arrutia, Francisco Amador Riera

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The meat industry generates large volumes of blood as a result of meat processing. Several industrial procedures have been implemented in order to treat this by-product, but are focused on the production of low-value products, and in many cases, blood is simply discarded as waste. Besides, in addition to economic interests, there is an environmental concern due to bloodborne pathogens and other chemical contaminants found in blood. Consequently, there is a dire need to find extensive uses for blood that can be both applicable to industrial scale and able to yield high value-added products. Blood has been recognized as an important source of protein. The main blood serum protein in mammals is serum albumin. One of the top trends in food market is functional foods. Among them, bioactive peptides can be obtained from protein sources by microbiological fermentation or enzymatic and chemical hydrolysis. Bioactive peptides are short amino acid sequences that can have a positive impact on health when administered. The main drawback for bioactive peptide production is the high cost of the isolation, purification and characterization techniques (such as chromatography and mass spectrometry) that make unaffordable the scale-up. On the other hand, membrane technologies are very suitable to apply to the industry because they offer a very easy scale-up and are low-cost technologies, compared to other traditional separation methods. In this work, the possibility of obtaining bioactive peptide fractions from serum albumin by means of a simple procedure of only 2 steps (hydrolysis and membrane filtration) was evaluated, as an exploratory study for possible industrial application. The methodology used in this work was, firstly, a tryptic hydrolysis of serum albumin in order to release the peptides from the protein. The protein was previously subjected to a thermal treatment in order to enhance the enzyme cleavage and thus the peptide yield. Then, the obtained hydrolysate was filtered through a nanofiltration/ultrafiltration flat rig at three different pH values with two different membrane materials, so as to compare membrane performance. The corresponding permeates were analyzed by liquid chromatography-tandem mass spectrometry technology in order to obtain the peptide sequences present in each permeate. Finally, different concentrations of every permeate were evaluated for their in vitro antihypertensive and antioxidant activities though ACE-inhibition and DPPH radical scavenging tests. The hydrolysis process with the previous thermal treatment allowed achieving a degree of hydrolysis of the 49.66% of the maximum possible. It was found that peptides were best transmitted to the permeate stream at pH values that corresponded to their isoelectric points. Best selectivity between peptide groups was achieved at basic pH values. Differences in peptide content were found between membranes and also between pH values for the same membrane. The antioxidant activity of all permeates was high compared with the control only for the highest dose. However, antihypertensive activity was best for intermediate concentrations, rather than higher or lower doses. Therefore, although differences between them, all permeates were promising regarding antihypertensive and antioxidant properties.

Keywords: bioactive peptides, bovine serum albumin, hydrolysis, membrane filtration

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Authors: Lukasz Szymanski, Zbigniew Kolacinski, Grzegorz Raniszewski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza, Karolina Przybylowska-Sygut, Ireneusz Majsterek, Zbigniew Kaminski, Justyna Fraczyk, Malgorzata Walczak, Beata Kolasinska, Adam Bednarek, Joanna Konka

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The aim of this work is to investigate the influence of electromagnetic field from the range of radio frequencies on the desired nanoparticles for cancer therapy. In the article, the development and demonstration of the method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nanocontainers. The methodology of the production carbon - ferromagnetic nanocontainers (FNCs) includes: The synthesis of carbon nanotubes, chemical, and physical characterization, increasing the content of a ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. The ferromagnetic nanocontainers were synthesised in CVD and microwave plasma system. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Pristine ferromagnetic carbon nanotubes are not suitable for application in medicine and biotechnology. Appropriate functionalization of ferromagnetic carbon nanotubes allows to receiving materials useful in medicine. Finally, a product contains folic acids on the surface of FNCs. The folic acid is a ligand of folate receptors – α which is overexpressed on the surface of epithelial tumours cells. It is expected that folic acids will be recognized and selectively bound by receptors presented on the surface of tumour cells. In our research, FNCs were covalently functionalized in a multi-step procedure. Ferromagnetic carbon nanotubes were oxidated using different oxidative agents. For this purpose, strong acids such as HNO3, or mixture HNO3 and H2SO4 were used. Reactive carbonyl and carboxyl groups were formed on the open sides and at the defects on the sidewalls of FNCs. These groups allow further modification of FNCs as a reaction of amidation, reaction of introduction appropriate linkers which separate solid surface of FNCs and ligand (folic acid). In our studies, amino acid and peptide have been applied as ligands. The last step of chemical modification was reaction-condensation with folic acid. In all reaction as coupling reagents were used derivatives of 1,3,5-triazine. The first trials in the device for hyperthermal RF generator have been done. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz. Obtained functionalized nanoparticles enabled to reach the temperature of denaturation tumor cells in given frequencies.

Keywords: cancer colon cells, carbon nanotubes, hyperthermia, ligands

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Authors: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal

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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.

Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma

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Authors: Z. Karahaliloğlu, E. Yalçın, M. Demirbilek, E.B. Denkbaş

Abstract:

Critical-sized bone defects caused by trauma, bone diseases, prosthetic implant revision or tumor excision cannot be repaired by physiological regenerative processes. Current orthopedic applications for critical-sized bone defects are to use autologous bone grafts, bone allografts, or synthetic graft materials. However, these strategies are unable to solve completely the problem, and motivate the development of novel effective biological scaffolds for tissue engineering applications and regenerative medicine applications. In particular, scaffolds combined with a variety of bio-agents as fundamental tools emerge to provide the regeneration of damaged bone tissues due to their ability to promote cell growth and function. In this study, a magnetic silk fibroin (SF) hydrogel scaffold was prepared by electrogelation process of the concentrated Bombxy mori silk fibroin (8 %wt) aqueous solution. For enhancement of osteoblast-like cells (SaOS-2) growth and adhesion, basal fibroblast growth factor (bFGF) were conjugated physically to the HSA-coated magnetic nanoparticles (Fe3O4) and magnetic SF e-gel scaffolds were prepared by incorporation of Fe3O4, HSA (human serum albumin)=Fe3O4 and HSA=Fe3O4-bFGF nanoparticles. HSA=Fe3O4, HSA=Fe3O4-bFGF loaded and bare SF e-gels scaffolds were characterized using scanning electron microscopy (SEM.) For cell studies, human osteoblast-like cell line (SaOS-2) was used and an MTT assay was used to assess the cytotoxicity of magnetic silk fibroin e-gel scaffolds and cell density on these surfaces. For the evaluation osteogenic activation, ALP (alkaline phosphatase), the amount of mineralized calcium, total protein and collagen were studied. Fe3O4 nanoparticles were successfully synthesized and bFGF was conjugated to HSA=Fe3O4 nanoparticles with %97.5 of binding yield which has a particle size of 71.52±2.3 nm. Electron microscopy images of the prepared HSA and bFGF incorporated SF e-gel scaffolds showed a 3D porous morphology. In terms of water uptake results, bFGF conjugated HSA=Fe3O4 nanoparticles has the best water absorbability behavior among all groups. In the in-vitro cell culture studies realized using SaOS-2 cell line, the coating of Fe3O4 nanoparticles surface with a protein enhance the cell viability and HSA coating and bFGF conjugation, the both have an inductive effect in the cell proliferation. One of the markers of bone formation and osteoblast differentiation, according to the ALP activity and total protein results, HSA=Fe3O4-bFGF loaded SF e-gels had significantly enhanced ALP activity. Osteoblast cultured HSA=Fe3O4-bFGF loaded SF e-gels deposited more calcium compared with SF e-gel. The proposed magnetic scaffolds seem to be promising for bone tissue regeneration and used in future work for various applications.

Keywords: basic fibroblast growth factor (bFGF), e-gel, iron oxide nanoparticles, silk fibroin

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Authors: Sandra Smieszek, Jonathan Haines

Abstract:

Introduction: Numerous research efforts have focused on searching for ‘longevity genes’. However, attempting to decipher the genetic component of the longevous phenotype have resulted in limited success and the mechanisms governing longevity remain to be explained. We conducted a genome-wide homozygosity analysis (GWHA) of the founder population of the Amish community in central Ohio. While genome-wide association studies using unrelated individuals have revealed many interesting longevity associated variants, these variants are typically of small effect and cannot explain the observed patterns of heritability for this complex trait. The Amish provide a large cohort of extended kinships allowing for in depth analysis via family-based approach excellent population due to its. Heritability of longevity increases with age with significant genetic contribution being seen in individuals living beyond 60 years of age. In our present analysis we show that the heritability of longevity is estimated to be increasing with age particularly on the paternal side. Methods: The present analysis integrated both phenotypic and genotypic data and led to the discovery of a series of variants, distinct for stratified populations across ages and distinct for paternal and maternal cohorts. Specifically 5437 subjects were analyzed and a subset of 893 successfully genotyped individuals was used to assess CHIP heritability. We have conducted the homozygosity analysis to examine if homozygosity is associated with increased risk of living beyond 90. We analyzed AMISH cohort genotyped for 614,957 SNPs. Results: We delineated 10 significant regions of homozygosity (ROH) specific for the age group of interest (>90). Of particular interest was ROH on chromosome 13, P < 0.0001. The lead SNPs rs7318486 and rs9645914 point to COL4A2 and our lead SNP. COL25A1 encodes one of the six subunits of type IV collagen, the C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. The second region of interest points to IRS2. Furthermore we built a classifier using the obtained SNPs from the significant ROH region with 0.945 AUC giving ability to discriminate between those living beyond to 90 years of age and beyond. Conclusion: In conclusion our results suggest that a history of longevity does indeed contribute to increasing the odds of individual longevity. Preliminary results are consistent with conjecture that heritability of longevity is substantial when we start looking at oldest fifth and smaller percentiles of survival specifically in males. We will validate all the candidate variants in independent cohorts of centenarians, to test whether they are robustly associated with human longevity. The identified regions of interest via ROH analysis could be of profound importance for the understanding of genetic underpinnings of longevity.

Keywords: regions of homozygosity, longevity, SNP, Amish

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Authors: B. Petrović, L. Rutonjski, M. Baucal, M. Teodorović, O. Čudić, B. Basarić

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Purpose/Objective: Radiotherapy treatment planning requires use of CT simulator, in order to acquire CT images. The overall performance of CT simulator determines the quality of radiotherapy treatment plan, and at the end, the outcome of treatment for every single patient. Therefore, it is strongly advised by international recommendations, to set up a quality control procedures for every machine involved in radiotherapy treatment planning process, including the CT scanner/ simulator. The overall process requires number of tests, which are used on daily, weekly, monthly or yearly basis, depending on the feature tested. Materials/Methods: Two phantoms were used: a dedicated phantom CIRS 062QA, and a QA phantom obtained with the CT simulator. The examined CT simulator was Siemens Somatom Definition as Open, dedicated for radiation therapy treatment planning. The CT simulator has a built in software, which enables fast and simple evaluation of CT QA parameters, using the phantom provided with the CT simulator. On the other hand, recommendations contain additional test, which were done with the CIRS phantom. Also, legislation on ionizing radiation protection requires CT testing in defined periods of time. Taking into account the requirements of law, built in tests of a CT simulator, and international recommendations, the intitutional QC programme for CT imulator is defined, and implemented. Results: The CT simulator parameters evaluated through the study were following: CT number accuracy, field uniformity, complete CT to ED conversion curve, spatial and contrast resolution, image noise, slice thickness, and patient table stability.The following limits are established and implemented: CT number accuracy limits are +/- 5 HU of the value at the comissioning. Field uniformity: +/- 10 HU in selected ROIs. Complete CT to ED curve for each tube voltage must comply with the curve obtained at comissioning, with deviations of not more than 5%. Spatial and contrast resultion tests must comply with the tests obtained at comissioning, otherwise machine requires service. Result of image noise test must fall within the limit of 20% difference of the base value. Slice thickness must meet manufacturer specifications, and patient stability with longitudinal transfer of loaded table must not differ of more than 2mm vertical deviation. Conclusion: The implemented QA tests gave overall basic understanding of CT simulator functionality and its clinical effectiveness in radiation treatment planning. The legal requirement to the clinic is to set up it’s own QA programme, with minimum testing, but it remains user’s decision whether additional testing, as recommended by international organizations, will be implemented, so to improve the overall quality of radiation treatment planning procedure, as the CT image quality used for radiation treatment planning, influences the delineation of a tumor and calculation accuracy of treatment planning system, and finally delivery of radiation treatment to a patient.

Keywords: CT simulator, radiotherapy, quality control, QA programme

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Authors: Alyaa Farouk Ibrahim, Gehan ElSayed, Ola Mamdouh, Nazek AbdelGhany

Abstract:

Background: Primary health care (PHC) can be considered the first contact between the patient and the health care system. It includes all the basic health care services to be provided to the community. Patient's satisfaction regarding health care has often improved the provision of care, also considered as one of the most important measures for evaluating the health care. Objective: This study aims to identify patient’s satisfaction with services provided at the primary health care settings in Alexandria. Setting: Seven primary health care settings representing the seven zones of Alexandria governorate were selected randomly and included in the study. Subjects: The study comprised 386 patients attended the previously selected settings at least twice before the time of the study. Tools: Two tools were utilized for data collection; sociodemographic characteristics and health status structured interview schedule and patient satisfaction scale. Reliability test for the scale was done using Cronbach's Alpha test, the result of the test ranged between 0.717 and 0.967. The overall satisfaction was computed and divided into high, medium, and low satisfaction. Results: Age of the studied sample ranged between 19 and 62 years, more than half (54.2%) of them aged 40 to less than 60 years. More than half (52.8%) of the patients included in the study were diabetics, 39.1% of them were hypertensive, 19.2% had cardiovascular diseases, the rest of the sample had tumor, liver diseases, and orthopedic/neurological disorders (6.5%, 5.2% & 3.2%, respectively). The vast majority of the study group mentioned high satisfaction with overall service cost, environmental conditions, medical staff attitude and health education given at the PHC settings (87.8%, 90.7%, 86.3% & 90.9%, respectively), however, medium satisfaction was mostly reported concerning medical checkup procedures, follow-up data and referral system (41.2%, 28.5% & 28.9%, respectively). Score level of patient satisfaction with health services provided at the assessed Primary health care settings proved to be significantly associated with patients’ social status (P=0.003, X²=14.2), occupation (P=0.011, X²=11.2), and monthly income (P=0.039, X²=6.50). In addition, a significant association was observed between score level of satisfaction and type of illness (P=0.007, X²=9.366), type of medication (P=0.014, X²=9.033), prior knowledge about the health center (P=0.050, X²=3.346), and highly significant with the administrative zone (P=0.001, X²=55.294). Conclusion: The current study revealed that overall service cost, environmental conditions, staff attitude and health education at the assessed primary health care settings gained high patient satisfaction level, while, medical checkup procedures, follow-up, and referral system caused a medium level of satisfaction among assessed patients. Nevertheless, social status, occupation, monthly income, type of illness, type of medication and administrative zones are all factors influencing patient satisfaction with services provided at the health facilities.

Keywords: patient satisfaction, chronic illness, quality of health service, quality of service indicators

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Authors: Serap Durkut, A. Eser Elcin, Y. Murat Elcin

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Stimuli-sensitive polymeric hydrogels have received extensive attention in the biomedical field due to their sensitivity to physical and chemical stimuli (temperature, pH, ionic strength, light, etc.). This study describes the rheological properties of a novel thermoresponsive poly(N-vinylcaprolactam)-g-collagen hydrogel. In the study, we first synthesized a facile and novel synthetic carboxyl group-terminated thermo-responsive poly(N-vinylcaprolactam)-COOH (PNVCL-COOH) via free radical polymerization. Further, this compound was effectively grafted with native collagen, by utilizing the covalent bond between the carboxylic acid groups at the end of the chains and amine groups of the collagen using cross-linking agent (EDC/NHS), forming PNVCL-g-Col. Newly-formed hybrid hydrogel displayed novel properties, such as increased mechanical strength and thermoresponsive characteristics. PNVCL-g-Col showed low critical solution temperature (LCST) at 38ºC, which is very close to the body temperature. Rheological studies determine structural–mechanical properties of the materials and serve as a valuable tool for characterizing. The rheological properties of hydrogels are described in terms of two dynamic mechanical properties: the elastic modulus G′ (also known as dynamic rigidity) representing the reversible stored energy of the system, and the viscous modulus G″, representing the irreversible energy loss. In order to characterize the PNVCL-g-Col, the rheological properties were measured in terms of the function of temperature and time during phase transition. Below the LCST, favorable interactions allowed the dissolution of the polymer in water via hydrogen bonding. At temperatures above the LCST, PNVCL molecules within PNVCL-g-Col aggregated due to dehydration, causing the hydrogel structure to become dense. When the temperature reached ~36ºC, both the G′ and G″ values crossed over. This indicates that PNVCL-g-Col underwent a sol-gel transition, forming an elastic network. Following temperature plateau at 38ºC, near human body temperature the sample displayed stable elastic network characteristics. The G′ and G″ values of the PNVCL-g-Col solutions sharply increased at 6-9 minute interval, due to rapid transformation into gel-like state and formation of elastic networks. Copolymerization with collagen leads to an increase in G′, as collagen structure contains a flexible polymer chain, which bestows its elastic properties. Elasticity of the proposed structure correlates with the number of intermolecular cross-links in the hydrogel network, increasing viscosity. However, at 8 minutes, G′ and G″ values sharply decreased for pure collagen solutions due to the decomposition of the elastic and viscose network. Complex viscosity is related to the mechanical performance and resistance opposing deformation of the hydrogel. Complex viscosity of PNVCL-g-Col hydrogel was drastically changed with temperature and the mechanical performance of PNVCL-g-Col hydrogel network increased, exhibiting lesser deformation. Rheological assessment of the novel thermo-responsive PNVCL-g-Col hydrogel, exhibited that the network has stronger mechanical properties due to both permanent stable covalent bonds and physical interactions, such as hydrogen- and hydrophobic bonds depending on temperature.

Keywords: poly(N-vinylcaprolactam)-g-collagen, thermoresponsive polymer, rheology, elastic modulus, stimuli-sensitive

Procedia PDF Downloads 231