Search results for: ion-beam cancer therapy

Authors: Mariam Khaled, Noha Farag, Ghada Mohamed Abdel Salam, Khaled Abu-Aisha, Mohamed El-Azizi

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Gastric and colorectal cancers are among the most frequent causes of cancer-associated mortalities in Africa. They have been considered as a global public health concern, as nearly one million new cases are reported per year. IL-1β is a pro-inflammatory cytokine-produced by activated macrophages and monocytes- and a member of the IL-1 family. The inactive IL-1β precursor is cleaved and activated by caspase-1 enzyme, which itself is activated by the assembly of intracellular structures defined as NLRP3 (Nod Like receptor P3) inflammasomes. Activated IL-1β stimulates the Interleukin-1 receptor type-1 (IL-1R1), which is responsible for the initiation of a signal transduction pathway leading to cell proliferation. It has been proven that the IL-1β gene is a highly polymorphic gene in which single nucleotide polymorphisms (SNPs) may affect its expression. It has been previously reported that SNPs including base transitions between C and T at positions, -511 (C-T; dbSNP: rs16944) and -31 (C-T; dbSNP: rs1143627), from the transcriptional start site, contribute to the pathogenesis of gastric and colorectal cancers by affecting IL-1β levels. Altered production of IL-1β due to such polymorphisms is suspected to stimulate an amplified inflammatory response and promote Epithelial Mesenchymal Transition leading to malignancy. Allele frequency distribution of the IL-1β-31 and -511 SNPs, in different populations, and their correlation to the incidence of gastric and colorectal cancers, has been intriguing to researchers worldwide. The current study aims to investigate allele distributions of the IL-1β SNPs among gastric and colorectal cancers Egyptian patients. In order to achieve to that, 89 Biopsy and surgical specimens from the antrum and corpus mucosa of chronic gastritis subjects and gastric and colorectal carcinoma patients was collected for DNA extraction followed by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). The amplified PCR products of IL-1β-31C > T and IL-1β-511T > C were digested by incubation with the restriction endonuclease enzymes ALu1 and Ava1. Statistical analysis was carried out to determine the allele frequency distribution in the three studied groups. Also, the effect of the IL-1β -31 and -511 SNPs on nuclear factor binding was analyzed using Fluorescence Electrophoretic Mobility Shift Assay (EMSA), preceded by nuclear factor extraction from gastric and colorectal tissue samples and LPS stimulated monocytes. The results of this study showed that a significantly higher percentage of Egyptian gastric cancer patients have a homozygous CC genotype at the IL-1β-31 position and a heterozygous TC genotype at the IL-1β-511 position. Moreover, a significantly higher percentage of the colorectal cancer patients have a homozygous CC genotype at the IL-1β-31 and -511 positions as compared to the control group. In addition, the EMSA results showed that IL-1β-31C/T and IL-1β-511T/C SNPs do not affect nuclear factor binding. Results of this study suggest that the IL-1β-31 C/T and IL-1β-511 T/C may be correlated to the incidence of gastric cancer in Egyptian patients; however, similar findings couldn’t be proven in the colorectal cancer patients group for the IL-1β-511 T/C SNP. This is the first study to investigate IL-1β -31 and -511 SNPs in the Egyptian population.

Keywords: colorectal cancer, Egyptian patients, gastric cancer, interleukin-1β, single nucleotide polymorphisms

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Authors: Kaouther Bergaui, Nafaa Reguigui, Charles Gary

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Characterization and the applications of deuterium-deuterium (DD) neutron generator developed by Adelphie technology and acquired by the National Centre of Nuclear Science and Technology (NCNST) were presented in this work. We study the performance of the neutron generator in terms of neutron yield, production efficiency, and the ionic current as a function of the acceleration voltage at various RF powers. We provide the design and optimization of the PGNAA chamber and thus give insight into the capabilities of the planned PGNAA facility. Additional non-destructive techniques were studied employing the DD neutron generator, such as PGNAA and neutron radiography: The PGNAA is used for determining the concentration of 10B in Si and SiO2 matrices by using a germanium detector HPGe and the results obtained are compared with PGNAA system using a Sodium Iodide detector (NaI (Tl)); Neutron radiography facility was tested and simulated, using a camera device CCD and simulated by the Monte Carlo code; and the explosive detection system (EDS) also simulated using the Monte Carlo code. The study allows us to show that the new models of DD neutron generators are feasible and that superior-quality neutron beams could be produced and used for various applications. The feasibility of Boron neutron capture therapy (BNCT) for cancer treatment using a neutron generator was assessed by optimizing Beam Shaping Assembly (BSA) on a phantom using Monte-Carlo (MCNP6) simulations.

Keywords: neutron generator deuterium-deuterium, Monte Carlo method, radiation, neutron flux, neutron activation analysis, born, neutron radiography, explosive detection, BNCT

Procedia PDF Downloads 184

Authors: D. O. Miranda, L. R. Azevedo, J. F. C. Cordeiro, A. H. Dos Santos, S. F. Lisboa, F. S. Guimarães, G. S. Bisson

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Background: The Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer death in the world. The prevalence of psychiatric-disorders among CRC patients, mainly depression, is high, resulting in impaired quality of life and side effects of primary treatment. High levels of proinflammatory cytokines at tumor microenvironment is a feature of CRC and the literature suggests that those mediators could contribute to the development of psychiatric disorders. Nevertheless, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and is still not well understood. Therefore, the aim of the present study was to test the hypothesis that depressive-like behavior in an experimental model of CCR induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was correlated to proinflammatory profile in the periphery and in the brain. Methods: Colorectal carcinogenesis was induced in adult C57BL/6 mice (n=12) by administration of MNNG (5mg/kg, 0.1ml/intrarectal instillation) 2 times a week, for 2 week. Control group (n=12) received saline (0.1ml/intrarectal instillation). Eight weeks after beginning of MNNG administration animals were submitted to the forced swim test (FST) and the sucrose preference test for evaluation, respectively, of depressive- and anhedonia-like behaviors. After behavioral evaluation, the colon was collected and brain regions dissected (cortex-C, striatum-ST and hippocampus-HIP) for posterior evaluation of cytokine levels (IL-1β, IL-10, IL-17, and CX3CL1) by ELISA. Results: MNNG induced depressive-like behavior, represented by increased immobility time in the FST (Student t test, p < 0.05) and lower sucrose preference (Student t test, p < 0.05). Moreover, there were increased levels of IL-1β, IL-17 and CX3CL1 in the colonic tissue (Student t test, p < 0.05) and in the brain (IL-1 β in the ST and HIP, Student t test, p < 0.05; IL-17 and CX3CL1 in the C and HIP, p < 0.05). IL-10 levels, in contrast, were decreased in both the colon (p < 0.05) and the brain (C and HIP, p < 0.05). Conclusions: The results obtained in the present work support the notion that tumor growth induces neuroinflammation in stress-related brain regions and depressive-like behavior, which could be related to the high incidence of depression in colorectal carcinogenesis. This work have important clinical and research implications, taken into account that cytokine levels may be a marker promissory for the developing depression in CRC patients. New therapeutic strategies to assist in alleviating mental suffering in cancer patients might result from a better understanding of the role of cytokines in the pathophysiology of depression in these subjects.

Keywords: cytokines, brain, depression, colorectal cancer

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Authors: Ankita Shukla, Tiratha Raj Singh

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Colorectal cancer (CRC) imposes serious mortality burden worldwide and it has been increasing for past consecutive years. Continuous efforts have been made so far to diagnose the disease condition and to identify the root cause for it. In this study, we performed the pathway level as well as the differential gene expression studies for CRC. We analyzed the gene expression profile GSE24514 from Gene Expression Omnibus (GEO) along with the gene pathways involved in the CRC. This analysis helps us to understand the behavior of the genes that have shown differential expression through their targeted pathways. Pathway analysis for the targeted genes covers the wider area which therefore decreases the possibility to miss the significant ones. This will prove to be beneficial to expose the ones that have not been given attention so far. Through this analysis, we attempt to understand the various neighboring genes that have close relationship to the targeted one and thus proved to be significantly controlling the CRC. It is anticipated that the identified hub and neighboring genes will provide new directions to look at the pathway level differently and will be crucial for the regulatory processes of the disease.

Keywords: mismatch repair, microsatellite instability, carcinogenesis, morbidity

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Authors: Fereydoon Bondarian, Samira Shaygan

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Today, many nutritionists recommend the consumption of plants, fruits, and vegetables to provide the antioxidants needed by the body because the use of plant antioxidants usually causes fewer side effects and better treatment. Natural antioxidants increase the power of plasma antioxidants and reduce the incidence of some diseases, such as cancer. Bad lifestyles and environmental factors play an important role in increasing the incidence of cancer. In this study, different extracts of white teas taken from two types of tea available in Iran (clone 100 and Chinese hybrid) due to the presence of a hydroxyl functional group in their structure to inhibit free radicals and anticancer properties, using 3 aqueous, methanolic and aqueous-methanolic methods were used. The total polyphenolic content was calculated using the Folin-Ciocalcu method, and the percentage of inhibition and trapping of free radicals in each of the extracts was calculated using the DPPH method. With the help of high-performance liquid chromatography, a small amount of each catechin in the tea samples was obtained. Clone 100 white tea was found to be the best sample of tea in terms of all the examined attributes (total polyphenol content, antioxidant properties, and individual amount of each catechin). The results showed that aqueous and aqueous-methanolic extracts of Clone 100 white tea have the highest total polyphenol content with 27.59±0.08 and 36.67±0.54 (equivalent gallic acid per gram dry weight of leaves), respectively. Due to having the highest level of different groups of catechin compounds, these extracts have the highest property of inhibiting and trapping free radicals with 66.61±0.27 and 71.74±0.27% (mg/l) of the extracted sample against ascorbic acid). Using the MTT test, the inhibitory effect of clone 100 white tea extract in inhibiting the growth of HCT-116 colon cancer cells was investigated and the best time and concentration treatments were 500, 150 and 1000 micrograms in 8, 16 and 24 hours, respectively. To investigate gene expression changes, selected genes, including tumorigenic genes, proto-oncogenes, tumor suppressors, and genes involved in apoptosis, were selected and analyzed using the real-time PCR method and in the presence of concentrations obtained for white tea. White tea extract at a concentration of 1000 μg/ml 3 times 16, 8, and 24 hours showed the highest growth inhibition in cancer cells with 53.27, 55.8, and 86.06%. The concentration of 1000 μg/ml aqueous extract of white tea under 24-hour treatment increased the expression of tumor suppressor genes compared to the normal sample.

Keywords: catechin, gene expression, suppressor genes, colon cell line

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Authors: Khusboo Agrawal, S. Saraf

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Quercetin, a flavonol provides a cellular protection against UV induced oxidative damages due to its excellent free radical scavenging activity and direct pro-apoptopic effect on tumor cells. However, its topical use is limited due to its unfavorable physicochemical properties. The present study was aimed to evaluate the potential of mesoporous silica nanoparticles as topical carrier system for quercetin delivery. Complexes of quercetin with mesoporous silica was prepared with different weight ratios and characterized by thermo gravimetric analysis, X-ray diffraction, high resolution TEM, FT-IR spectroscopy, zeta potential measurements and differential scanning calorimetry The protective effect of this vehicle on UV-induced degradation of the quercetin was investigated revealing a certain positive influence of the inclusion on the photostability over time. Epidermal accumulation and transdermal permeation of this molecule were ex vivo evaluated by using Franz diffusion cells. The immobilization of Quercetin in mesoporous silica nanoparticles (MSNs) increased the stability without undermining the antioxidant efficacy.

Keywords: cancer, MSNs, quercetin, topical delivery

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Authors: Asif Bilal, Fouzia Tanvir, Sibtain Ahmad

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Estrogen receptor alpha, also known as estrogen receptor-1, is highly involved in risk of mammary carcinoma. The objectives of this study were to identify non-synonymous SNPs of estrogen receptor and their association with breast cancer and to identify the chemotherapeutic responses of phytochemicals against it via in-silico study design. For this purpose, different online tools. to identify pathogenic SNPs the tools were SIFT, Polyphen, Polyphen-2, fuNTRp, SNAP2, for finding disease associated SNPs the tools SNP&GO, PhD-SNP, PredictSNP, MAPP, SNAP, MetaSNP, PANTHER, and to check protein stability Mu-Pro, I-Mutant, and CONSURF were used. Post-translational modifications (PTMs) were detected by Musitedeep, Protein secondary structure by SOPMA, protein to protein interaction by STRING, molecular docking by PyRx. Seven SNPs having rsIDs (rs760766066, rs779180038, rs956399300, rs773683317, rs397509428, rs755020320, and rs1131692059) showing mutations on I229T, R243C, Y246H, P336R, Q375H, R394S, and R394H, respectively found to be completely deleterious. The PTMs found were 96 times Glycosylation; 30 times Ubiquitination, a single time Acetylation; and no Hydroxylation and Phosphorylation were found. The protein secondary structure consisted of Alpha helix (Hh) is (28%), Extended strand (Ee) is (21%), Beta turn (Tt) is 7.89% and Random coil (Cc) is (44.11%). Protein-protein interaction analysis revealed that it has strong interaction with Myeloperoxidase, Xanthine dehydrogenase, carboxylesterase 1, Glutathione S-transferase Mu 1, and with estrogen receptors. For molecular docking we used Asiaticoside, Ilekudinuside, Robustoflavone, Irinoticane, Withanolides, and 9-amin0-5 as ligands that extract from phytochemicals and docked with this protein. We found that there was great interaction (from -8.6 to -9.7) of these ligands of phytochemicals at ESR1 wild and two mutants (I229T and R394S). It is concluded that these SNPs found in ESR1 are involved in breast cancer and given phytochemicals are highly helpful against breast cancer as chemotherapeutic agents. Further in vitro and in vivo analysis should be performed to conduct these interactions.

Keywords: breast cancer, ESR1, phytochemicals, molecular docking

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Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko

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During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.

Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity

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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: Patricia O. Carvalho, Marcia C. F. Messias, Salvador Sanchez Vinces, Caroline F. A. Gatinoni, Vitor P. Iordanu, Carlos A. R. Martinez

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Lipidomics methods are widely used in the identification and validation of disease-specific biomarkers and therapy response evaluation. The present study aimed to identify a panel of potential lipid biomarkers to evaluate response to neoadjuvant chemoradiotherapy in rectal adenocarcinoma (RAC). Liquid chromatography–mass spectrometry (LC-MS)-based untargeted lipidomic was used to profile human serum samples from patients with clinical stage T2 or T3 resectable RAC, after and before chemoradiotherapy treatment. A total of 28 blood plasma samples were collected from 14 patients with RAC who recruited at the São Francisco University Hospital (HUSF/USF). The study was approved by the ethics committee (CAAE 14958819.8.0000.5514). Univariate and multivariate statistical analyses were applied to explore dysregulated metabolic pathways using untargeted lipidic profiling and data mining approaches. A total of 36 statistically significant altered lipids were identified and the subsequent partial least-squares discriminant analysis model was both cross validated (R2, Q2) and permutated. Lisophosphatidyl-choline (LPC) plasmalogens containing palmitoleic and oleic acids, with high variable importance in projection score, showed a tendency to be lower after completion of chemoradiotherapy. Chemoradiotherapy seems to change plasmanyl-phospholipids levels, indicating that these lipids play an important role in the RAC pathogenesis.

Keywords: lipidomics, neoadjuvant chemoradiotherapy, plasmalogens, rectal adenocarcinoma

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Authors: Garima Joshi, Pratap Sharan, V. Sreenivas, Nand Kumar, Kameshwar Prasad, Ashima N. Wadhawan

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Schizophrenia is a debilitating disorder and is marked by cognitive impairment, which deleteriously impacts the social and professional functioning along with the quality of life of the patients and the caregivers. Often the cognitive symptoms are in their prodromal state and worsen as the illness progresses; they have proven to have a good predictive value for the prognosis of the illness. It has been shown that intensive cognitive rehabilitation (CR) leads to improvements in the healthy as well as cognitively-impaired subjects. As the majority of population in India falls in the lower to middle socio-economic status and have low education levels, using the existing packages, a majority of which are developed in the West, for cognitive rehabilitation becomes difficult. The use of technology is also restricted due to the high costs involved and the limited availability and familiarity with computers and other devices, which pose as an impedance for continued therapy. Cognitive rehabilitation in India uses a plethora of retraining methods for the patients with schizophrenia targeting the functions of attention, information processing, executive functions, learning and memory, and comprehension along with Social Cognition. Psychologists often have to follow an integrative therapy approach involving social skills training, family therapy and psychoeducation in order to maintain the gains from the cognitive rehabilitation in the long run. This paper reviews the methodologies and cognitive retaining programs used in India. It attempts to elucidate the evolution and development of methodologies used, from traditional paper-pencil based retraining to more sophisticated neuroscience-informed techniques in cognitive rehabilitation of deficits in schizophrenia as home-based or supervised and guided programs for cognitive rehabilitation.

Keywords: schizophrenia, cognitive rehabilitation, neuropsychological interventions, integrated approached to rehabilitation

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Authors: Ma. Cecilia D. Licuan

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The pandemic situation continues to affect the lives of many people, including children with disabilities and their families, globally, especially in developing countries like the Philippines. The operations of health programs, industries, and economic sectors, as well as academic training institutions, are still challenged in terms of operations and delivery of services. The academic community of the Physical Therapy program is not spared by this circumstance. The restriction posted by the quarantine policies nearly terminated the onsite delivery of training programs for the senior internship level, which challenged the academic institutions to implement flexible learning programs to ensure the continuity of the instructional and learning processes with full consideration of safety and compliance to health protocols. This study aimed to develop a benchmark model that can be used by tertiary-level health institutions in the implementation of the Pediatric Senior Clinical Internship Training Program using Telerehabilitation. It is a descriptive-qualitative paper that utilized documentary analysis and focused on explaining the design, development, and implementation processes used by De La Salle Medical and Health Sciences Institute – College of Rehabilitation Sciences (DLSMHSI-CRS) Physical Therapy Department in its Pediatric Cluster Senior Clinical Internship Training Program covering the pandemic years spanning from the academic year 2020- 2021 to present anchored on needs analysis based on documentary reviews. Results of the study yielded the determination of the Pediatric Telerehabilitation Model; declaration of developed training program outcomes and thrusts and content; explanation of the process integral to the training program’s pedagogy in implementation; and the evaluation procedures conducted for the program. Since the study did not involve human participants, ethical considerations on the use of documents for review were done upon the endorsement of the management of the DLSMHSI-CRS to conduct the study. This paper presents the big picture of how a tertiary-level health sciences institution in the Philippines embraced the senior clinical internship challenges through the operations of its telerehabilitation program. It specifically presents the design, development and implementation processes used by De La Salle Medical and Health Sciences Institute – College of Rehabilitation Sciences Physical Therapy Department in its Pediatric Cluster Senior Clinical Internship Training Program, which can serve as a benchmark model for other institutions as they continue to serve their stakeholders amidst the pandemic.

Keywords: pediatric physical therapy, telerehabilitation, clinical internship, pandemic

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Authors: Sean Yao Zu Kong, Khong Yik Chew

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Introduction: We described a case report of the successful use of advanced surgical techniques in a patient with recurrent breast cancer who underwent a wide resection including the hemi-sternum, clavicle, multiple ribs, and a lobe of the lung due to tumor involvement. This extensive resection exposed critical structures, requiring a creative approach to reconstruction. To address this complex chest wall reconstruction, a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap were successfully utilized. The use of a free vascularized bone flap allowed for rapid osteointegration and resistance against osteoradionecrosis after adjuvant radiation, while a four-zone tram flap allowed for reconstruction of both the chest wall and breast mound. Although limited recipient vessels made free flaps challenging, the free fibula flap served as both a bony reconstruction and vascular conduit, supercharged with the distal peroneal artery and veins of the peroneal artery from the fibula graft. Our approach highlights the potential of advanced surgical techniques to improve outcomes in complex cases of chest wall reconstruction in patients with recurrent breast cancer, which is becoming increasingly relevant as breast cancer incidence rates increases. Case presentation: This report describes a successful reconstruction of a patient with recurrent breast cancer who required extensive resection, including the anterior chest wall, clavicle, and sternoclavicular joint. Challenges arose due to the loss of accessory muscles and the non-rigid rib cage, which could lead to compromised ventilation and instability. A free fibula osteocutaneous flap and a four-zone TRAM flap with vascular supercharging were utilized to achieve long-term stability and function. The patient has since fully recovered, and during the review, both flaps remained viable, and chest mound reconstruction was satisfactory. A planned nipple/areolar reconstruction was offered pending the patient’s decision after adjuvant radiotherapy. Conclusion: In conclusion, this case report highlights the successful use of innovative surgical techniques in addressing a complex case of recurrent breast cancer requiring extensive resection and radical reconstruction. Our approach, utilized a combination of a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap, demonstrates the potential for advanced techniques in chest wall reconstruction to minimize complications and ensure long-term stability and function. As the incidence of breast cancer continues to rise, it is crucial that healthcare professionals explore and utilize innovative techniques to improve patient outcomes and quality of life.

Keywords: free fibula flap, rectus abdominis musculocutaneous flap, post-adjuvant radiotherapy, reconstructive surgery, malignancy

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Authors: Jose G. Tshikuka, Goabaone Rankgoane-Pono, Mgaywa G. M. D. Magafu, Julius C. Mwita, Tiny Masupe, Fortunat M. Kandanda, Shimeles G. Hamda, Roy Tapera, Mooketsi Molefi, John T. Tlhakanelo

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Background: Factors associated with overweight and obesity among antiretroviral therapy (ART) recipients have not been sufficiently studied in Botswana. We aimed to study (i) the prevalence and trends in overweight/obesity by duration of exposure to ART among recipients, (ii) changes in body mass index (BMI) categories among recipients before ART initiation (BMI-1) and after ART initiation (BMI-2), (iii) associations between ART and overweight/obesity and (iv) factors associated with BMI changes among ART recipients. Methods: A 12 years retrospective record-based review was conducted. Factors potentially associated with BMI change among patients after at least three years of ART exposure were examined using multiple regression model. Adjusted odds ratios (AOR) and their 95% confidence intervals (CIs) were computed. ART regimens, duration of exposure to ART, and recipients’ demographic and biomedical characteristics including the presence or absence of diabetes mellitus related comorbidities (DRC) were investigated as potential factors associated with overweight/obesity. Results: Twenty-nine percent of recipients were overweight, 16.6% had obesity of whom 2.4% were morbidly-obese at the last clinic visit. Overweight/obesity recipients were more likely to be female, to have DRC and less likely to have nadir CD4 count or CD4 count between 201 – 249 cells/mm³. Neither the first-line nor the second-, third-line ART regimens predicted overweight/obesity more than the other and neither did the duration of exposure to ART. No significant linear trends were observed in the prevalence of overweight/obesity by the duration of exposure to ART. Conclusions: These results indicate that overweight/obesity seen among ART recipients is not directly induced by ART. ART used CD4 and/or DRC pathway to induce overweight/obesity seen among recipients; suggesting that, weight gain documented herein is likely a reflection of improved health status that mirrors trends in the general population or a DRC related effect. Weight management programs may be important components of HIV care.

Keywords: overweight/obesity, recipients of antiretroviral therapy, HIV/AIDS, Botswana

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: Marwan Jarrah, Nadia Nugrush, Sukainah Ali, Areej Allawzi

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This research article investigates how illnesses (different types and severity) are expressed in Arabic discourse with a particular focus on input coming from Colloquial Jordanian Arabic (CJA). Drawing on a corpus of naturally occurring conversations, this article offers evidence that illnesses are predominantly expressed through two different sets of expressive strategies, namely direct expressive strategies (DES) and indirect expressive strategies (IES). The latter are exclusively used when cancer and mental health disorders are targeted. IES include the substitution of the name of the illness with some religious expressions (e.g., ʔallah ʔijdʒi:rna ‘May Allah keeps us safe’) or certain terms especially when cancer is meant (e.g., haðˤa:k ʔil-maraðˤ ‘that disease’). On the other hand, DES are used in conjunction with other illnesses (e.g., heart, kidneys, diabetes, etc.), regardless of their severity. DES include specific formulas that remarkably mention the name of the inflicted organ (e.g., [with-SOMEONE the ORGAN] as in ʕinduh ʔil-qalb ‘lit. with-him the heart’ meaning ‘He has a heart disease). We discuss the effects of religious beliefs and local norms and values in determining the use of these strategies.

Keywords: Illnesses, pragmatics, expressive strategies, religion

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Authors: Kapoor Anurag, Sharma Pradeep, Mittal K Kailash, Kumar Ajai, Jawad Kalbe, Amit Kumar Singh

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Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant tumour on a global scale. Limited research has been conducted on tumour markers in oral cancer, and additional evaluation is required for several tumour producers that show clinical promise. The present study aimed to find out the co-relation of β-2 Microglobulin and Lipid Bound Sialic Acid in oral carcinoma patients. Methodology: The present case-control study was carried out on 35 patients with histopathologically confirmed OSCC and 35 age-matched controls. Serum concentrations of 2-Microglobulin and Total Sialic Acid (TSA) in the participants were determined via ELISA and spectrophotometric technique, respectively. Results: The OSCC group consisted of 20 males and 15 females, with an average age of 58 years, while the control group comprised 18 males and 17 females, with an average age of 55 years. Elevated levels of β2-microglobulin (3.87±0.12) and LSA (73.57±2.42) were observed in OSCC patients compared to controls (2.25±0.18; 65.21±2.06, respectively). Further examination based on smoking status revealed a significant increase in both β2-microglobulin and LSA levels among smokers compared to non-smokers (p < 0.05). Conclusion: The study suggests a notable association between higher levels of β2-microglobulin and LSA in oral squamous cell carcinoma (OSCC) patients who smoke compared to non-smokers. This observation leads to a hypothesis that this disparity could potentially serve as a significant contributing factor to the advancement of oral cancer.

Keywords: biochemistry human cancer, human, oral carcinoma, marker

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Authors: Zakia Belhadj, Bing He, Hua Zhang, Xueqing Wang, Wenbing Dai, Qiang Zhang

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Mononuclear phagocyte system (MPS) forms an abominable obstacle hampering the tumor delivery efficiency of nanoparticles. Passively targeted nanocarriers have received clinical approval over the past 20 years. However, none of the actively targeted nanocarriers have entered clinical trials. Thus it is important to endue effective targeting ability to actively targeted approaches by overcoming biological barriers to nanoparticle drug delivery. Here, it presents that an Esomeprazole-based preconditioning strategy for regulating nanocarrier-MPS interaction to substantially prolong circulation time and enhance tumor targeting of nanoparticles. In vitro, the clinically approved proton pump inhibitor Esomeprazole “ESO” was demonstrated to reduce interactions between macrophages and subsequently injected targeted vesicles by interfering with their lysosomal trafficking. Of note, in vivo studies demonstrated that ESO pretreatment greatly decreased the liver and spleen uptake of c(RGDm7)-modified vesicles, highly enhanced their tumor accumulation, thereby provided superior therapeutic efficacy of c(RGDm7)-modified vesicles co-loaded with Doxorubicin (DOX) and Gefitinib (GE). This MPS-preconditioning strategy using ESO provides deeper insights into regulating nanoparticles interaction with the phagocytic system and enhancing their cancer cells' accessibility for anticancer therapy.

Keywords: esomeprazole (ESO), mononuclear phagocyte system (MPS), preconditioning strategy, targeted lipid vesicles

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Authors: Ian Omung'a

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Breast cancer remains to be one of the deadliest cancers for women worldwide, with the risk of developing tumors being as high as 50 percent in Sub-Saharan African countries like Kenya. With as many as 42 percent of these cases set to be diagnosed late when cancer has metastasized and or the prognosis has become terminal, Full Field Digital [FFD] Mammography remains an effective screening technique that leads to early detection where in most cases, successful interventions can be made to control or eliminate the tumors altogether. FFD Mammograms have been proven to multiply more effective when used together with Computer-Aided Detection and Diagnosis [CADe] systems, relying on algorithmic implementations of Deep Learning techniques in Computer Vision to carry out deep pattern recognition that is comparable to the level of a human radiologist and decipher whether specific areas of interest in the mammogram scan image portray abnormalities if any and whether these abnormalities are indicative of a benign or malignant tumor. Within this paper, we review emergent Deep Learning techniques that will prove relevant to the development of State-of-The-Art FFD Mammogram CADe systems. These techniques will span self-supervised learning for context-encoded occlusion, self-supervised learning for pre-processing and labeling automation, as well as the creation of a standardized large-scale mammography dataset as a benchmark for CADe systems' evaluation. Finally, comparisons are drawn between existing practices that pre-date these techniques and how the development of CADe systems that incorporate them will be different.

Keywords: breast cancer diagnosis, computer aided detection and diagnosis, deep learning, whole mammogram classfication, ultrasound classification, computer vision

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Authors: Harshadkumar Rajgor, Jeff Butterworth

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Background: Barretts oesophagus increases the risk of developing oesophageal adenocarcinoma. Over the last 40 years, there has been a 6 fold increase in the incidence of oesophageal adenocarcinoma in the western world and the incidence rates are increasing at a greater rate than cancers of the colon, breast and lung. Endoscopic mucosal resection (EMR) is a relatively new technique being used by 2 centres in the greater midlands cancer network. EMR can be used for curative or staging purposes, for high-grade dysplasia’s and T1 tumours of the oesophagus. EMR is also suitable for those who are deemed high risk for oesophagectomy. EMR has a recurrence rate of 21% according to the Wiesbaden data. Method: A retrospective study of prospectively collected data was carried out involving 24 patients who had EMR for curative or staging purposes. Complications of residual or recurrent disease following EMR that required further treatment were investigated. Results: In 54% of cases residual or recurrent disease was suspected. 96% of patients were given clear and concise information regarding their diagnosis of high-grade dysplasia or T1 tumours. All 24 patients consulted the same specialist healthcare team. Conclusion: EMR is a safe and effective treatment for patients who have high-grade dysplasia and T1NO tumours. In 54% of cases residual or recurrent disease was suspected. Initially, only single resections were undertaken. Multiple resections are now being carried out to reduce the risk of recurrence. Complications from EMR remain low in this series and consisted of a single episode of post procedural bleeding.

Keywords: endoscopic mucosal resection, oesophageal dysplasia, T1 tumours, cancer network

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Authors: Leander Van Neste, Kirk Wojno

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The innate immune system reacts to foreign insult in several unique ways, one of which is phagocytosis of perceived threats such as cancer, bacteria, and viruses. The goal of this study was to look for evidence of phagocytosed RNA from tumor cells in circulating monocytes. While all monocytes possess phagocytic capabilities, the non-classical CD14+/FCGR3A+ monocytes and the intermediate CD14++/FCGR3A+ monocytes most actively remove threatening ‘external’ cellular materials. Purified CD14-positive monocyte samples from fourteen patients recently diagnosed with clinically localized prostate cancer (PCa) were investigated by single-cell RNA sequencing using the 10X Genomics protocol followed by paired-end sequencing on Illumina’s NovaSeq. Similarly, samples were processed and used as controls, i.e., one patient underwent biopsy but was found not to harbor prostate cancer (benign), three young, healthy men, and three men previously diagnosed with prostate cancer that recently underwent (curative) radical prostatectomy (post-RP). Sequencing data were mapped using 10X Genomics’ CellRanger software and viable cells were subsequently identified using CellBender, removing technical artifacts such as doublets and non-cellular RNA. Next, data analysis was performed in R, using the Seurat package. Because the main goal was to identify differences between PCa patients and ‘control’ patients, rather than exploring differences between individual subjects, the individual Seurat objects of all 21 patients were merged into one Seurat object per Seurat’s recommendation. Finally, the single-cell dataset was normalized as a whole prior to further analysis. Cell identity was assessed using the SingleR and cell dex packages. The Monaco Immune Data was selected as the reference dataset, consisting of bulk RNA-seq data of sorted human immune cells. The Monaco classification was supplemented with normalized PCa data obtained from The Cancer Genome Atlas (TCGA), which consists of bulk RNA sequencing data from 499 prostate tumor tissues (including 1 metastatic) and 52 (adjacent) normal prostate tissues. SingleR was subsequently run on the combined immune cell and PCa datasets. As expected, the vast majority of cells were labeled as having a monocytic origin (~90%), with the most noticeable difference being the larger number of intermediate monocytes in the PCa patients (13.6% versus 7.1%; p<.001). In men harboring PCa, 0.60% of all purified monocytes were classified as harboring PCa signals when the TCGA data were included. This was 3-fold, 7.5-fold, and 4-fold higher compared to post-RP, benign, and young men, respectively (all p<.001). In addition, with 7.91%, the number of unclassified cells, i.e., cells with pruned labels due to high uncertainty of the assigned label, was also highest in men with PCa, compared to 3.51%, 2.67%, and 5.51% of cells in post-RP, benign, and young men, respectively (all p<.001). It can be postulated that actively phagocytosing cells are hardest to classify due to their dual immune cell and foreign cell nature. Hence, the higher number of unclassified cells and intermediate monocytes in PCa patients might reflect higher phagocytic activity due to tumor burden. This also illustrates that small numbers (~1%) of circulating peripheral blood monocytes that have interacted with tumor cells might still possess detectable phagocytosed tumor RNA.

Keywords: circulating monocytes, phagocytic cells, prostate cancer, tumor immune response

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Authors: Anne Giles

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Trauma is generally defined as an experience, or multiple experiences, overwhelming a person's ability to cope. Over time, many people recover from the neurobiological, physical, and emotional effects of trauma on their own. For some people, however, troubling symptoms develop over time that can result in distress and disability. This cluster of symptoms is classified as Post-traumatic Stress Disorder (PTSD). People who meet the criteria for PTSD and other trauma-related disorder diagnoses often hold a set of understandable but unfounded beliefs about traumatic events that cause undue suffering. Becoming aware of unhelpful beliefs—termed "cognitive distortions"—and challenging them is the realm of Cognitive Behavior Therapy (CBT). A form of CBT found by researchers to be especially effective for PTSD is Cognitive Processing Therapy (CPT). Through the compassionate use of CPT, people identify, examine, challenge, and relinquish unhelpful beliefs, thereby reducing symptoms and suffering. Widely-held cultural beliefs can interfere with the progress of recovery from trauma-related disorders. Although highly revered, largely unquestioned, and often stabilizing, cultural beliefs can be founded in simplistic, dichotomous thinking, i.e., things are all right, or all wrong, all good, or all bad. The reality, however, is nuanced and complex. After studying examples of cultural beliefs from China and the United States and how these might interfere with trauma recovery, trauma counselors can help clients derive criteria for preserving helpful beliefs, discover, examine, and jettison unhelpful beliefs, reduce trauma symptoms, and live their lives more freely and fully.

Keywords: cognitive processing therapy (CPT), cultural beliefs, post-traumatic stress disorder (PTSD), trauma recovery

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Authors: Sylwia K. Naliwajko, Renata Markiewicz-Zukowska, Justyna Moskwa, Krystyna Gromkowska-Kepka, Konrad Mielcarek, Patryk Nowakowski, Katarzyna Socha, Anna Puscion-Jakubik, Maria H. Borawska

Abstract:

Glioblastoma (grade IV WHO) is a rapidly progressive brain tumor with very high morbidity and mortality. The vast malignant gliomas are not curable despite the therapy (surgical, radiotherapy, chemotherapy) and patients seek alternative or complementary treatments. Patients often use cannabidiol (CBD) oil as an alternative therapy of glioblastoma. CBD is one of the cannabinoids, an active component of Cannabis sativa. THC (Δ9-tetrahydrocannabinol) can be addictive, and in many countries CBD oil without THC ( < 0,2%) is available. Propolis produced by bees from the resin collected from trees has antiglioma properties in vitro and can be used as a supplement in complementary therapy of gliomas. The aim of this study was to examine the influence of extract from CBD oil in combination with propolis extract on two glioblastoma cell lines. The MTT (Thiazolyl Blue Tetrazolium Bromide) test was used to determine the influence of CBD oil extract and polish propolis extract (PPE) on the viability of glioblastoma cell lines – U87MG and LN18. The cells were incubated (24, 48 and 72 h) with CBD oil extract and PPE. CBD extract was used in concentration 1, 1.5 and 3 µM and PPE in 30 µg/mL. The data were presented compared to the control. The statistical analysis was performed using Statistica v. 13.0 software. CBD oil extract in concentrations 1, 1.5 and 3 µM did not inhibit the viability of U87MG and LN18 cells (viability more than 90% cells compared to the control). There was no dose-response viability, and IC50 value was not recognized. PPE in the concentration of 30 µg/mL time-dependently inhibited the viability of U87MG and LN18 cell line (after 48 h the viability as a percent of the control was 59,7±6% and 57,8±7%, respectively). In a combination of CBD with PPE, the viability of the treated cells was similar to PPE used alone (58,2±7% and 56,5±9%, respectively). CBD oil extract did not show anti-glioma activity and in combination with PPE did not change the activity of PPE.

Keywords: anticancer, cannabidiol, cell line, glioblastoma

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Authors: N. Dunleavy, E. Lovemore, K. Siljeur, D. Jackson, M. Hendricks, M. Hoosain, N. Plastow, S. Marais

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Background: The work requirements of sewing machine operators cause physical and emotional strain. Past ergonomic interventions have been provided to alleviate physical concerns; however, a holistic, multimodal intervention was needed to improve these factors. Aim: The study aimed to examine the effect of an occupational therapy programme on sewing machine operators’ pain, mental health, and productivity within a factory in the South African context. Methods: A pilot randomised control trial was conducted with 22 sewing machine operators within a single factory. Stratified randomisation was used to determine the experimental (EG) and control groups (CG), using measures for pain intensity, level of depression (mental health), and productivity rates as stratification variables. The EG received the multimodal intervention, incorporating education, seating adaptations, and mental health intervention. In three months, the CG will receive the same intervention. Pre- and post-intervention testing have occurred with upcoming three- and six-month follow-ups. Results: Immediate results indicate a statistically significant decrease in pain in both experimental and control groups; no change in productivity scores and depression between the two groups. This may be attributed to external factors. The values for depression further showed no statistical significance between the two groups and within pre-and post-test results. The Statistical Program for Social Sciences (SPSS) version-24 was used as the data analysis testing, where all the tests will be evaluated at a 5% significance level. Contribution of research: The research adds to the body of knowledge informing the Occupational Therapy role in work settings, providing evidence on the effectiveness of workplace-based multimodal interventions. Conclusion: The study provides initial data on the effectiveness of a pilot randomised control trial on pain and mental health in South Africa. Results indicated no quantitative change between the experimental and control groups; however, qualitative data suggest a clinical significance of the findings.

Keywords: ergonomics programme, occupational therapy, sewing machine operators, workplace-based multimodal interventions

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Authors: Yuexin Liu, Gordon B. Mills, Russell R. Broaddus, John N. Weinstein

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The lethality of endometrioid endometrial cancer (EEC) is primarily attributable to the high-stage diseases. However, there are no available biomarkers that predict EEC patient staging at the time of diagnosis. We aim to develop a predictive scheme to help in this regards. Using reverse-phase protein array expression profiles for 210 EEC cases from The Cancer Genome Atlas (TCGA), we constructed a Protein Scoring of EEC Staging (PSES) scheme for surgical stage prediction. We validated and evaluated its diagnostic potential in an independent cohort of 184 EEC cases obtained at MD Anderson Cancer Center (MDACC) using receiver operating characteristic curve analyses. Kaplan-Meier survival analysis was used to examine the association of PSES score with patient outcome, and Ingenuity pathway analysis was used to identify relevant signaling pathways. Two-sided statistical tests were used. PSES robustly distinguished high- from low-stage tumors in the TCGA cohort (area under the ROC curve [AUC]=0.74; 95% confidence interval [CI], 0.68 to 0.82) and in the validation cohort (AUC=0.67; 95% CI, 0.58 to 0.76). Even among grade 1 or 2 tumors, PSES was significantly higher in high- than in low-stage tumors in both the TCGA (P = 0.005) and MDACC (P = 0.006) cohorts. Patients with positive PSES score had significantly shorter progression-free survival than those with negative PSES in the TCGA (hazard ratio [HR], 2.033; 95% CI, 1.031 to 3.809; P = 0.04) and validation (HR, 3.306; 95% CI, 1.836 to 9.436; P = 0.0007) cohorts. The ErbB signaling pathway was most significantly enriched in the PSES proteins and downregulated in high-stage tumors. PSES may provide clinically useful prediction of high-risk tumors and offer new insights into tumor biology in EEC.

Keywords: endometrial carcinoma, protein, protein scoring of EEC staging (PSES), stage

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Authors: Kasra Afsahi, Maryam Soheilifar

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COVID-19 has been associated with stroke and neurological complications. The patient was a 59-year- old male who presented with sudden left hemiparesis and diplopia due to cavernous sinus thrombosis (CST) on 28/03/2020. The COVID-19 test was positive. Multislice CT (MSCT) showed ischemic infarction. He underwent surgical sinectomy 9 days after admission. Physiotherapy began for him in August 2020. Our game-based virtual reality (VR) technology developed for stroke patients was based on upper extremity exercises and function for stroke. After 6 weeks of VR therapy plus conventional physiotherapy exercises (18 sessions, three times per week, 60 minutes each session), there were significant improvements in Brunnstrom Motor Recovery Stage (from “4” to “5”), Fugl-Meyer Scale score of upper extremity section (from 49 to 54), and Modified Barthel Index (from15 to 18). There were no adverse effects. This case with stroke post-COVID-19 due to the CST showed the usefulness of VR therapy used as an adjunct to conventional physiotherapy in improving affected upper extremity.

Keywords: COVID-19, stroke, virtual reality, rehabilitation

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Authors: A. H. Bekhet, N. Helmy

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Background: Physical therapists are knowledgeable in treatment and prevention of musculoskeletal injuries; however, they have occupational musculoskeletal injuries because Physical therapy profession requires effort that may lead to work-related musculoskeletal disorders. No previous studies among physical therapists have been reported in Egypt. We aim to assess the prevalence and risk factors of musculoskeletal disorders among physical therapist’s seniors versus internship students. Method: We conducted a cross-sectional study in faculty of physical therapy Cairo university Prevalence and risk factors of musculoskeletal injuries were assessed using self-administered questionnaire with closed-ended questions. Seniors therapist was defined as a physical therapist with more than 5 years of work experience. Data were analyzed using SPSS 22.0 for Windows. Results: The study included 106 physical therapists (Junior = 72; senior = 34), the mean age of senior therapists was 30.1 (SD 6.3) years and junior therapists were 22.8 (SD 2.4). Female subjects constituted 83.9% of the studied sample. The mean hours of contact with patients was higher among junior therapists 6.4 (SD 2.6) vs. 5.7 (SD 2.1) among senior therapists. The prevalence of a musculoskeletal injury, once or more in their lifetime, was significantly higher among senior therapists (86% vs. 66.7%; p = 0.04). The highest risk factor in increasing the symptoms of the injury among junior therapists was maintaining a position for a prolonged period of time at 28% while performing manual therapy techniques was the highest risk factor among senior therapists at 32%. 53% of senior therapists have limited their patient contact time as a result of their injury in comparison to 25% of junior therapists (p = 0.09). Conclusion: the presented study shows that the prevalence of musculoskeletal injuries, once or more in their lifetime, is significantly higher among senior therapists.

Keywords: musculoskeletal injuries, occupational injuries, physical therapists, work related disorders

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Authors: Joanna Marie A. Paulino-Morente, Vaneza Valentina L. Penolio, Grace Sabado

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Ovarian cancer is extremely hard to diagnose in its early stages, and those afflicted at the time of diagnosis are typically asymptomatic and in the late stages of the disease, with metastasis to other organs. Ovarian cancers often occur sporadically, with only 5% associated with hereditary mutations. Mutations in the BRCA1 and BRCA2 tumor suppressor genes have been found to be responsible for the majority of hereditary ovarian cancers. One type of ovarian tumor is Malignant Mixed Mullerian Tumor (MMMT), which is a very rare and aggressive type, accounting for only 1% of all ovarian cancers. Reported is a case of a 43-year-old G3P3 (3003), who came into our institution due to a 2-month history of difficulty of breathing. Family history reveals that her eldest and younger sisters both died of ovarian malignancy, with her younger sister having a histopathology report of endometrioid ovarian carcinoma, left ovary stage IIIb. She still has 2 asymptomatic sisters. Physical examination pointed to pleural effusion of right lung, and presence of bilateral ovarian new growth, which had a Sassone score of 13. Admitting Diagnosis was G3P3 (3003), Ovarian New Growth, bilateral, Malignant; Pleural effusion secondary to malignancy. BRCA was requested to establish a hereditary mutation; however, the patient had no funds. Once the patient was stabilized, TAHBSO with surgical staging was performed. Intraoperatively, the pelvic cavity was occupied by firm, irregularly shaped ovaries, with a colorectal metastasis. Microscopic sections from both ovaries and the colorectal metastasis had pleomorphic tumor cells lined by cuboidal to columnar epithelium exhibiting glandular complexity, displaying nuclear atypia and increased nuclear-cytoplasmic ratio, which are infiltrating the stroma, consistent with the features of Malignant Mixed Mullerian Tumor, since MMMT is composed histologically of malignant epithelial and sarcomatous elements. In conclusion, discussed is the clinic-pathological feature of a patient with primary ovarian Malignant Mixed Mullerian Tumor, a rare malignancy comprising only 1% of all ovarian neoplasms. Also, by understanding the hereditary ovarian cancer syndromes and its relation to this patient, it cannot be overemphasized that a comprehensive family history is really fundamental for early diagnosis. The familial association of the disease, given that the patient has two sisters who were diagnosed with an advanced stage of ovarian cancer and succumbed to the disease at a much earlier age than what is reported in the general population, points to a possible hereditary syndrome which occurs in only 5% of ovarian neoplasms. In a low-resource setting, being in a third world country, the following will be recommended for monitoring and/or screening women who are at high risk for developing ovarian cancer, such as the remaining sisters of the patient: 1) Physical examination focusing on the breast, abdomen, and rectal area every 6 months. 2) Transvaginal sonography every 6 months. 3) Mammography annually. 4) CA125 for postmenopausal women. 5) Genetic testing for BRCA1 and BRCA2 will be reserved for those who are financially capable.

Keywords: BRCA, hereditary breast-ovarian cancer syndrome, malignant mixed mullerian tumor, ovarian cancer

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Authors: F. Ruiz-Navarro, M. Matzner, G. Kobinia

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Background: Cerebral palsy (CP) encompasses the largest group of childhood movement disorders, the patterns and severity varies widely. Today, the management focuses only on a rehabilitation therapy that tries to secure the functions remained and prevents complications. However the treatments are not aimed to cure the disease. Stem cells (SCs) transplant via intrathecal is a new approach to the disease. Method: Our aim was to performed a pilot study under the condition of unproven treatment on clinical practice to assessed the safety and efficacy of Neuron Point-of-care Stem cell Therapy (N-POCST), an ambulatory procedure of autologous bone marrow derived SCs (BM-SCs) harvested from the posterior superior iliac crest undergo an on-site cell separation for intrathecal infusion via lumbar puncture. Results: 82 patients were treated in a period of 28 months, with a follow-up after 6 months. They had a mean age of 6,2 years old and male predominance (65,9%). Our preliminary results show that: A. No patient had any major side effects, B. Only 20% presented mild headache due to LP, C. 53% of the patients had an improvement in spasticity, D. 61% improved the coordination abilities, 23% improved the motor function, 15% improved the speech, 23% reduced the number of convulsive events with the same doses or less doses of anti-convulsive medication and 94% of the patients report a subjective general improvement. Conclusions: These results support previous worldwide publications that described the safety and effectiveness of autologous BM-SCs transplant for patients wit CP.

Keywords: autologous transplant, cerebral palsy, point of care, childhood movement disorders

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Authors: Senthil Rajan Dharmalingam, Shamala Nadaraju, Srinivasan Ramamurthy

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Doxorubicin is the most widely used anticancer drugs in chemotherapy treatment. However, problems related to the development of multidrug resistance (MDR) and acute cardiotoxicity have led researchers to investigate alternative forms of administering doxorubicin for cancer therapy. Several methods have been attempted to overcome MDR, including the co-administration of a chemosensitizer inhibiting the efflux caused by ATP binding cassette transporters with anticancer drugs, and the bypass of the efflux mechanism. Co encapsulation of doxorubicin (Dox) and cyclosporine A (CSA) into poly (DL-lactide-co-glycolide) nanoparticles was emulsification-solvent evaporation method using polyvinyl alcohol as emulsion stabilizers. The Dox-CSA loaded nanoparticles were evaluated for particle size, zeta potential and PDI by light scattering analysis and thermal characterizations by differential scanning calorimetry (DSC). Loading efficiency (LE %) and in-vitro dissolution samples were evaluated by developed and validated HPLC method. The optimum particle size obtained is 298.6.8±39.4 nm and polydispersity index (PDI) is 0.098±0.092. Zeta potential is found to be -29.9±4.23. Optimum pH to increase Dox LE% was found 7.1 which gave 42.5% and 58.9% increase of LE% for pH 6.6 and pH 8.6 compared respectively. LE% achieved for Dox is 0.07±0.01 % and CSA is 0.09±0.03%. Increased volume of PVA and weight of PLGA shows increase in size of nanoparticles. DSC thermograms showed shift in the melting peak for the nanoparticles compared to Dox and CSA indicating encapsulation of drugs. In conclusion, these preliminary studies showed the feasibility of PLGA nanoparticles to entrap Dox and CSA and require future in-vivo studies to be performed to establish its potential.

Keywords: doxorubicin, cyclosporine, PLGA, nanoparticles

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