Search results for: pediatric cancer

Authors: Danyi Wang, Andrew Schriefer, Dennis O'Rourke, Brajendra Kumar, Yang Liu, Fei Zhong, Juergen Scheuenpflug, Zheng Feng

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Purpose: It has been recognized that the microbiome plays critical roles in disease pathogenesis, including cancer, autoimmune disease, and multiple sclerosis. To develop a clinical-grade assay for exploring microbiome-derived clinical biomarkers across disease areas, a two-phase approach is implemented. 1) Identification of the optimal sample preparation reagents using pre-mixed bacteria and healthy donor stool samples coupled with proprietary Sigma-Aldrich® bioinformatics solution. 2) Exploratory analysis of patient samples for enabling precision medicine. Study Procedure: In phase 1 study, we first compared the 16S sequencing results of two ATCC® microbiome standards (MSA 2002 and MSA 2003) across five different extraction kits (Kit A, B, C, D & E). Both microbiome standards samples were extracted in triplicate across all extraction kits. Following isolation, DNA quantity was determined by Qubit assay. DNA quality was assessed to determine purity and to confirm extracted DNA is of high molecular weight. Bacterial 16S ribosomal ribonucleic acid (rRNA) amplicons were generated via amplification of the V3/V4 hypervariable region of the 16S rRNA. Sequencing was performed using a 2x300 bp paired-end configuration on the Illumina MiSeq. Fastq files were analyzed using the Sigma-Aldrich® Microbiome Platform. The Microbiome Platform is a cloud-based service that offers best-in-class 16S-seq and WGS analysis pipelines and databases. The Platform and its methods have been extensively benchmarked using microbiome standards generated internally by MilliporeSigma and other external providers. Data Summary: The DNA yield using the extraction kit D and E is below the limit of detection (100 pg/µl) of Qubit assay as both extraction kits are intended for samples with low bacterial counts. The pre-mixed bacterial pellets at high concentrations with an input of 2 x106 cells for MSA-2002 and 1 x106 cells from MSA-2003 were not compatible with the kits. Among the remaining 3 extraction kits, kit A produced the greatest yield whereas kit B provided the least yield (Kit-A/MSA-2002: 174.25 ± 34.98; Kit-A/MSA-2003: 179.89 ± 30.18; Kit-B/MSA-2002: 27.86 ± 9.35; Kit-B/MSA-2003: 23.14 ± 6.39; Kit-C/MSA-2002: 55.19 ± 10.18; Kit-C/MSA-2003: 35.80 ± 11.41 (Mean ± SD)). Also, kit A produced the greatest yield, whereas kit B provided the least yield. The PCoA 3D visualization of the Weighted Unifrac beta diversity shows that kits A and C cluster closely together while kit B appears as an outlier. The kit A sequencing samples cluster more closely together than both the other kits. The taxonomic profiles of kit B have lower recall when compared to the known mixture profiles indicating that kit B was inefficient at detecting some of the bacteria. Conclusion: Our data demonstrated that the DNA extraction method impacts DNA concentration, purity, and microbial communities detected by next-generation sequencing analysis. Further microbiome analysis performance comparison of using healthy stool samples is underway; also, colorectal cancer patients' samples will be acquired for further explore the clinical utilities. Collectively, our comprehensive qualification approach, including the evaluation of optimal DNA extraction conditions, the inclusion of positive controls, and the implementation of a robust qualified bioinformatics pipeline, assures accurate characterization of the microbiota in a complex matrix for deciphering the deep biology and enabling precision medicine.

Keywords: 16S rRNA sequencing, analytical validation, bioinformatics pipeline, metagenomics

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Authors: N. A. Ahmad Zubairi, H. Takaijudin, K. W. Yusof

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Pesticides have been used widely over the world in agriculture to protect from pests and reduce crop losses. However, it affects the environment with toxic chemicals. Exceed of toxic constituents in the ecosystem will result in bad side effects. The hydrological cycle is related to the existence of pesticides and heavy metal which it can penetrate through varieties of sources into the soil or water bodies, especially runoff. Therefore, proper mechanisms of pesticide and heavy metal removal should be studied to improve the quality of ecosystem free or reduce from unwanted substances. This paper reviews the use of treatment train and its mechanisms to minimize pesticides and heavy metal from agricultural runoff. Organochlorine (OCL) is a common pesticide that was found in the agricultural runoff. OCL is one of the toxic chemicals that can disturb the ecosystem such as inhibiting plants' growth and harm human health by having symptoms as asthma, active cancer cell, vomit, diarrhea, etc. Thus, this unwanted contaminant gives disadvantages to the environment and needs treatment system. Hence, treatment train by bioretention system is suitable because removal efficiency achieves until 90% of pesticide removal with selected vegetated plant and additive.

Keywords: pesticides, heavy metal, agricultural runoff, bioretention, mechanism removal, treatment train

Procedia PDF Downloads 166

Authors: Akash Bera, Suraj Singh, Jacinta Dsouza, Ramakrishna V. Hosur, Pushpa Mishra

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Ultraviolet C (UVC) radiation induces apoptosis in mammalian cells and it is suggested that the mechanism by which this occurs is the mitochondrial pathway of apoptosis through the release of cytochrome c from the mitochondria into the cytosol. The Bcl-2 family of proteins pro-and anti-apoptotic is the regulators of the mitochondrial pathway of apoptosis. Upon UVC irradiation, the proliferation of apoptosis is enhanced through the downregulation of the anti-apoptotic protein Bcl-xl and up-regulation of Bax. Although the participation of the Bcl-2 family of proteins in apoptosis appears responsive to UVC radiation, to the author's best knowledge, it is unknown how the structure and, effectively, the function of these proteins are directly impacted by UVC exposure. In this background, we present here a structural rationale for the effect of UVC irradiation in restoring apoptosis using two of the relevant proteins, namely, Bid-FL and Bcl-xl ΔC, whose solution structures have been reported previously. Using a variety of biophysical tools such as circular dichroism, fluorescence and NMR spectroscopy, we show that following UVC irradiation, the structures of Bcl-xlΔC and Bid-FL are irreversibly altered. Bcl-xLΔC is found to be more sensitive to UV exposure than Bid-FL. From the NMR data, dramatic structural perturbations (α-helix to β-sheet) are seen to occur in the BH3 binding region, a crucial segment of Bcl-xlΔC which impacts the efficacy of its interactions with pro-apoptotic tBid. These results explain the regulation of apoptosis by UVC irradiation. Our results on irradiation dosage dependence of the structural changes have therapeutic potential for the treatment of cancer.

Keywords: Bid, Bcl-xl, UVC, apoptosis

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Authors: Kevser Cakmak, Adrián Montesano, Lourdes Artigas, Marta Salla, Clara Mateu

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The main objective of this research is to explore the relational letter writing technique as an intervention in couple therapy for reconnecting couples with their values and ethical preferences. This is a recently developed therapeutic tool within the framework of Narrative Therapy that consists of two interviews and a letter writing task, in which a meta-conversation between the relationship itself, the couple members, and the therapists is fostered. Although this specific therapeutic technique can be used within the therapy process, in this case study, it is used as a brief stand-alone narrative intervention for a middle age heterosexual couple breast cancer survivor. Couple’s relational and personal wellbeing was monitored before, during, and after the intervention by means of the dyadic adjustment and the clinical outcomes in routine evaluation-outcome measure, respectively. The couple showed a significant improvement after the intervention in both levels. The content of the letter writing exercises was qualitatively analysed to explore the reconstruction of their ethical values. Results from both methods are integrated in order to get an in-depth perspective of the newly developed tool. The potential of the letter writing technique as stand-alone and as adjunct brief intervention is discussed.

Keywords: couple therapy, narrative therapy, psychotherapy tool, relational letter writing

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Authors: Onur Karaman, A. Gunes Tanir

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Photon radiation therapy used to treat cancer is one of the most important methods. However, photon beam collimator materials in Linear Accelerator (LINAC) head generally contains heavy elements is used and the interaction of bremsstrahlung photon with such heavy nuclei, the neutron can be produced inside the treatment rooms. In radiation therapy, neutron contamination contributes to the risk of secondary malignancies in patients, also physicians working in this field. Since the neutron is more dangerous than photon, it is important to determine neutron dose during radiotherapy treatment. In this study, it is aimed to analyze the effect of field size, distance from axis and depth on the amount of in-field and out-field neutron contamination for ElektaVmat accelerator with 18 MV nominal energy. The photon spectra at the distance of 75, 150, 225, 300 cm from target and on the isocenter of beam were scored for 5x5, 10x10, 20x20, 30x30 and 40x40 cm2 fields. Results demonstrated that the neutron spectra and dose are dependent on field size and distances. Beyond 225 cm of isocenter, the dependence of the neutron dose on field size is minimal. As a result, it is concluded that as the open field increases, neutron dose determined decreases. It is important to remember that when treating with high energy photons, the dose from contamination neutrons must be considered as it is much greater than the photon dose.

Keywords: radiotherapy, neutron contamination, linear accelerators, photon

Procedia PDF Downloads 351

Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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Authors: Huayang Yu, Nicola Ingram, David C. Green, Paul D. Thornton

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The dual stimuli-controlled release of doxorubicin from gel-embedded nanoparticles is reported. Non-cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)-b-poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH-responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin-loaded nanoparticles could be incorporated within a thermoresponsive poly(2-hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2-hydroxypropyl methacrylate) into aqueous solution. The combination of the poly(2-hydroxypropyl methacrylate) gel and poly(ethylene glycol)-b-poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near-complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in a non-acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site-specific release of chemotherapeutics.

Keywords: biodegradable, nanoparticle, polymer, thermoresponsive

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Authors: Jan F. Talts, Amit Saxena, Kåre Engkilde

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by anti-neoplastic agents, with a prevalence from 19 % to 85 %. Clinically, CIPN is a mostly sensory neuropathy leading to pain and to motor and autonomic changes. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors, especially because currently, there is no single effective method of preventing CIPN. Hearing loss is the most common form of sensory impairment in humans and can be caused by ototoxic chemical compounds such as chemotherapy (platinum-based antineoplastic agents).In rodents, single or repeated cisplatin injections induce peripheral neuropathy and hearing impairment mimicking human disorder, allowing studying the efficacy of new pharmacological candidates in chemotherapy-induced hearing loss and peripheral neuropathy. RNA sequencing data from full term amniotic fluid (TAF) mesenchymal stemcell (MSC) clones was used to identify neural-specific markers present on TAF-MSC. Several prospective neural markers were tested by flow cytometry on cultured TAF-MSC. One of these markers was used for cell-sorting using Tyto MACSQuant cell sorter, and the neural marker positive cell population was expanded for several passages to the final therapeutic product stage. Peripheral neuropathy and hearing loss was induced in mice by administration of cisplatin in three week-long cycles. The efficacy of neural-specific TAF-MSC in treating hearing loss and pain perception was evaluated by administration of three injections of 3 million cells/kg by intravenous route or three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment. Auditory brainstem responses (ABR) are electric potentials recorded from scalp electrodes, and the first ABR wave represents the summed activity of the auditory nerve fibers contacting the inner hair cells. For ABR studies, mice were anesthetized, then earphones were placed in the left ear of each mouse, an active electrode was placed in the vertex of the skull, a reference electrode under the skin of the mastoid bone, and a ground electrode in the neck skin. The stimuli consisted of tone pips of five frequencies (2, 4, 6, 12, 16, and 24 kHz) at various sound levels (from 0 to 90 dB) ranging to cover the mouse auditory frequency range. The von Frey test was used to assess the onset and maintenance of mechanical allodynia over time. Mice were placed in clear plexiglass cages on an elevated mesh floor and tested after 30 min of habituation. Mechanical paw withdrawal threshold was examined using an electronic von Frey anesthesiometer. Cisplatin groups treated with three injections of 3 million cells/kg by intravenous route and three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment presented, a significant increase of hearing acuity characterized by a decrease of ABR threshold and a decrease of neuropathic pain characterized by an increase of von Frey paw withdrawal threshold compared to controls only receiving cisplatin. This study shows that treatment with MSCselected for neural specificity presents significant positive efficacy on the chemotherapy-induced neuropathic pain and the chemotherapy-induced hearing loss.

Keywords: mesenchymal stem cell, peripheral neuropathy, amniotic fluid, regenerative medicine

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Authors: Tamer El-Messery, Beraat Ozcelik

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This study aimed to produce functional yogurt supplemented with microencapsulated krill oil as a source of omega 3, which is known, to maintain the normal brain function, reduce the risk of cancer, and preventing cardiovascular disease. Krill oil was mixed with black cumin oil (1:1) in order to increase its oxidative stability. β-caroteine (10 mg/100 ml) was used as a standard antioxidant. Maltodextrin (MD) was mixed with whey protein concentrate (WPC) and gum Arabic (GA) at the ratio of 8:2:0.5 ratios and used for microencapsulation of single or mixed oils. The microcapsules were dried by freeze and spray drying in order to maximize encapsulation efficiency and minimize lipid oxidation. The feed emulsions used for particle production were characterized for stability, viscosity and particle size, zeta potential, and oxidative stability. The oxidative stability for mixed krill oil and black cumin oil was the highest. The highest encapsulation efficiency was obtained using spray drying, which also showed the highest oxidative stability. The addition of encapsulated krill and black cumin oils (1:1) powder in yogurt manufacture reduced slightly effects on the development of acidity, textural parameters, and water holding capacity of yogurt as compared to control.

Keywords: Krill oil, black cumin oil, micro-encapsulation, oxidative stability, functional yogurt

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Authors: Fawad Ali, Muhammad Ateeq, Ikhtiar Khan

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Ground water, a major source of drinking water supply in Peshawar has been severely contaminated by leather tanning industry. Effluents from the tanneries contain high concentration of chromium besides several other chemical species. Release of untreated effluents from the tanning industry has severely damaged surface and ground water, agriculture soil as well as vegetables and crops. Chromium is a well-known carcinogenic and mutagenic agent. Once in the human food chain, it causes multiple problems to the exposed population including various types of cancer, skin dermatitis, and DNA damage. In order to assess the extent of chromium and other heavy metals contamination, water samples were analyzed for heavy metals using Graphite Furnace Atomic Absorption Spectrometer (GFAAS, Analyst 700, Perkin Elmer). Total concentration of chromium was above the permissible limit (0.048 mg/l) in 85% of the groundwater (drinking water) samples. The concentration of cobalt, manganese, cadmium, nickel, lead, zinc and iron was also determined in the ground water, surface water, agriculture soil, and vegetables samples from the affected area.

Keywords: heavy metals, soil, groundwater, tannery effluents, food chain

Procedia PDF Downloads 348

Authors: Juan Francisco Morales Arteaga, Simon Gluhar, Anela Kaurin, Domen Lestan

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Contaminated soils are recognized as one of the most pressing global environmental problems. As is one of the most hazardous elements: chronic exposure to arsenic has devastating effects on health, cardiovascular diseases, cancer, and eventually death. Pb, Zn and Cd are very highly toxic metals that affect almost every organ in the body. With this in mind, new technologies for soil remediation processes are urgently needed. Calcareous artificially contaminated soil containing 231 mg kg-1 As and historically contaminated with Pb, Zn and Cd was washed with a 1:1.5 solid-liquid ratio of 90 mM EDTA, 100 mM oxalic acid, and 50 mM sodium dithionite to remove 59, 75, 29, and 53% of As, Pb, Zn, and Cd, respectively. To reduce emissions of residual EDTA and chelated metals from the remediated soil, zero valent iron (ZVI) was added (1% w/w) to the slurry of the washed soil immediately prior to rinsing. Experimental controls were conducted without the addition of ZVI after remediation. The use of ZVI reduced metal leachability and minimized toxic emissions 21 days after remediation. After this time, NH4NO3 extraction was performed to determine the mobility of toxic elements in the soil. In addition, Unified Human BioaccessibilityMethod (UBM) was performed to quantify the bioaccessibility levels of metals in stimulated human gastric and gastrointestinal phases.

Keywords: soil remediation, soil science, soil washing, toxic metals removal

Procedia PDF Downloads 181

Authors: Abdolreza Esmaeilzadeh, Maryam Erfanmanesh, Sousan Ghasemi, Farzaneh Mohammadi

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Background: Hepatitis C Virus (HCV), a public health problem, is an enveloped, single-stranded RNA virus and a member of the Hepacivirus genus of the Flaviviridae family. Liver cancer, cirrhosis, and end-stage liver are the outcomes of chronic infection with HCV. HCV isolates show significant heterogeneity in genetics around the world. Therefore, determining HCV genotypes is a vital step in determining prognosis and planning therapeutic strategies. Materials and Methods: Serum samples of 136 patients were collected and analyzed for anti-HCV antibodies using ELISA (The enzyme-linked immunosorbent assay) method. Then, positive samples were exposed to RT-PCR, which was performed under standard condition. Afterwards, they investigated for genotyping using allele-specific PCR (AS-PCR), and HCV genotype 2.0 line probe assay (LiPA). Results: Samples indicated 216 bp bands on 2% agarose gel. Analyses of the results demonstrated that the most dominant subtype was 3a with frequency of 38.26% in Zanjan Province followed by subtypes of 1b, 1a, 2, and 4 with frequencies of 25.73%, 22.05%, 5.14%, and 4.41%, respectively. The frequency of unknown HCV genotypes was 4.41%. Conclusions: According to the results, it was found that HCV high prevalent genotype in Zanjan is subtype 3a. Analysis of the results provides identification of certain HCV genotypes, and these valuable findings could affect the type and duration of the treatment.

Keywords: anti-HCV antibody, Hepatitis C Virus (HCV), genotype, RT-PCR, AS-PCR

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Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das

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Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.

Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity

Procedia PDF Downloads 517

Authors: Faris Alkhalil, Rana Bitar, Amer Azaz, Hisham Natour, Noora Almeraikhi, Mohamad Miqdady

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Background: Children with liver transplantation are achieving very good survival and so there is now a need to concentrate on achieving good health in these patients and preventing disease. Immunosuppressive medications have side effects that need to be monitored and if possible avoided. Glucocorticoids and calcineurin inhibitors are detrimental to bone and mineral homeostasis in addition steroids can also affect linear growth. Steroid sparing regimes in renal transplant children has shown to improve children’s height. Aim: We aim to review the growth and bone health of children post liver transplant by measuring bone mineral density (BMD) using dual energy X-ray absorptiometry (DEXA) scan and assessing if there is a clear link between poor growth and impaired bone health and use of long term steroids. Subjects and Methods: This is a single centre retrospective Cohort study, we reviewed the medical notes of children (0-16 years) who underwent a liver transplantation between November 2000 to November 2016 and currently being followed at our centre. Results: 39 patients were identified (25 males and 14 females), the median transplant age was 2 years (range 9 months - 16 years), and the median follow up was 6 years. Four patients received a combined transplant, 2 kidney and liver transplant and 2 received a liver and small bowel transplant. The indications for transplant included, Biliary Atresia (31%), Acute Liver failure (18%), Progressive Familial Intrahepatic Cholestasis (15%), transplantable metabolic disease (10%), TPN related liver disease (8%), Primary Hyperoxaluria (5%), Hepatocellular carcinoma (3%) and other causes (10%). 36 patients (95%) were on a calcineurin inhibitor (34 patients were on Tacrolimus and 2 on Cyclosporin). The other three patients were on Sirolimus. Low dose long-term steroids was used in 21% of the patients. A considerable proportion of the patients had poor growth. 15% were below the 3rd centile for weight for age and 21% were below the 3rd centile for height for age. Most of our patients with poor growth were not on long term steroids. 49% of patients had a DEXA scan post transplantation. 21% of these children had low bone mineral density, one patient had met osteoporosis criteria with a vertebral fracture. Most of our patients with impaired bone health were not on long term steroids. 20% of the patients who did not undergo a DEXA scan developed long bone fractures and 50% of them were on long term steroid use which may suggest impaired bone health in these patients. Summary and Conclusion: The incidence of impaired bone health, although studied in limited number of patients; was high. Early recognition and treatment should be instituted to avoid fractures and improve bone health. Many of the patients were below the 3rd centile for weight and height however there was no clear relationship between steroid use and impaired bone health, reduced weight and reduced linear height.

Keywords: bone, growth, pediatric, liver, transplantation

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Authors: Atitallah Sofien, Bouyahia Olfa, Romdhani Meriam, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Traditional medicine refers to a diverse range of therapeutic practices and knowledge systems that have been employed by different cultures over an extended period to uphold and rejuvenate health. These practices can involve herbal remedies, acupuncture, massage, and alternative healing methods that deviate from conventional medical approaches. In Tunisia, we often use unidentified utensils to scratch the oral cavity internally in infants in order to widen the oral cavity for better breathing and swallowing. However, these practices can be risky and may jeopardize the patients' prognosis or even their lives. Aim: This is the case of a nine-month-old infant, admitted to the pediatric department and subsequently to the intensive care unit due to a peritonsillar abscess following the utilization of an unidentifiable tool to scrape the interior of the oral cavity. Case Report: This is a 9-month-old infant with no particular medical history, admitted for high respiratory distress and a fever persisting for 4 days. On clinical examination, he had a respiratory rate of 70 cycles per minute with an oxygen saturation of 97% and subcostal retractions, along with a heart rate of 175 beats per minute. His white blood cell count was 40,960/mm³, and his C-reactive protein was 250 mg/L. Given the severity of the clinical presentation, the infant was transferred to the intensive care unit, intubated, and mechanically ventilated. A cervical-thoracic CT scan was performed, revealing a ruptured 18 mm left peritonsillar abscess in the oropharynx associated with cellulitis of the retropharyngeal space. The oto-rhino-laryngoscopic examination revealed an asymmetry involving the left lateral wall of the oropharynx with the presence of a fistula behind the posterior pillar. Dissection of the collection cavity was performed, allowing the drainage of 2 ml of pus. The culture was negative. The patient received cefotaxime in combination with metronidazole and gentamicin for a duration of 10 days, followed by a switch to amoxicillin-clavulanic acid for 7 days. The patient was extubated after 4 days of treatment, and the clinical and radiological progress was favorable. Conclusions: Traditional medicine remains risky due to the lack of scientific evidence and the potential for injuries and transmission of infectious diseases, especially in children, who constitute a vulnerable population. Therefore, parents should consult healthcare professionals and rely on evidence-based care.

Keywords: children, peritonsillar abscess, traditional medicine, respiratory distress

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Authors: Hamidreza Jabal Ameli, Anahita Movahedi

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Purpose: In radionuclide therapy, radioactive atoms are coupled to monoclonal antibodies (mAbs) for treating cancer tumor while limiting radiation to healthy tissues. We know that tumoral and normal tissues are not equally sensitive to radiation. In fact, biological effects such as cellular repair processes or the presence of less radiosensitive cells such as hypoxic cells should be taken account. For this reason, in this paper, we want to calculate biological effect dose (BED) inside tumoral area and healthy cells around tumors. Methods: In this study, deposited doses of a radionuclide, gold-198, inside cells lattice and surrounding healthy tissues were calculated with Monte Carlo method. The elemental compositions and density of malignant and healthy tissues were obtained from ICRU Report 44. For reaching to real condition of oxygen effects, the necrosis and hypoxia area inside tumors has been assessed. Results: With regard to linear-quadratic expression which was defined in Monte Carlo, results showed that a large amount of BED is deposited in the well-oxygenated part of the hypoxia area compared to necrosis area. Moreover, there is a significant difference between the curves of absorbed dose with BED and without BED.

Keywords: biological dose, monte carlo, hypoxia, radionuclide therapy

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Authors: Mustafa M. Donma, Orkide Donma

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The number of indices developed for the evaluation of obesity both in adults and pediatric population is ever increasing. These indices are also used in cases with metabolic syndrome (MetS), mostly the ultimate form of morbid obesity. Aside from anthropometric measurements, formulas constituted using these parameters also find clinical use. These formulas can be listed as two groups; being weight-dependent and –independent. Some are extremely sophisticated equations and their clinical utility is questionable in routine clinical practice. The aim of this study is to compare presently available obesity indices and find the most practical one. Their associations with MetS components were also investigated to determine their capacities in differential diagnosis of morbid obesity with and without MetS. Children with normal body mass index (N-BMI) and morbid obesity were recruited for this study. Three groups were constituted. Age- and sex- dependent BMI percentiles for morbid obese (MO) children were above 99 according to World Health Organization tables. Of them, those with MetS findings were evaluated as MetS group. Children, whose values were between 85 and 15 were included in N-BMI group. The study protocol was approved by the Ethics Committee of the Institution. Parents filled out informed consent forms to participate in the study. Anthropometric measurements and blood pressure values were recorded. Body mass index, hip index (HI), conicity index (CI), triponderal mass index (TPMI), body adiposity index (BAI), body shape index (ABSI), body roundness index (BRI), abdominal volume index (AVI), waist-to-hip ratio (WHR) and waist circumference+hip circumference/2 ((WC+HC)/2) were the formulas examined within the scope of this study. Routine biochemical tests including fasting blood glucose (FBG), insulin (INS), triglycerides (TRG), high density lipoprotein-cholesterol (HDL-C) were performed. Statistical package program SPSS was used for the evaluation of study data. p<0.05 was accepted as the statistical significance degree. Hip index did not differ among the groups. A statistically significant difference was noted between N-BMI and MetS groups in terms of ABSI. All the other indices were capable of making discrimination between N-BMI-MO, N-BMI- MetS and MO-MetS groups. No correlation was found between FBG and any obesity indices in any groups. The same was true for INS in N-BMI group. Insulin was correlated with BAI, TPMI, CI, BRI, AVI and (WC+HC)/2 in MO group without MetS findings. In MetS group, the only index, which was correlated with INS was (WC+HC)/2. These findings have pointed out that complicated formulas may not be required for the evaluation of the alterations among N-BMI and various obesity groups including MetS. The simple easily computable weight-independent index, (WC+HC)/2, was unique, because it was the only index, which exhibits a valuable association with INS in MetS group. It did not exhibit any correlation with other obesity indices showing associations with INS in MO group. It was concluded that (WC+HC)/2 was pretty valuable practicable index for the discrimination of MO children with and without MetS findings.

Keywords: children, insulin, metabolic syndrome, obesity indices

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Authors: M. Dabirinezhad, M. Bayat Pour, A. Dabirinejad

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In 2020, the technology was introduced to solve some of the deficiencies of direct digital radiology. SDDR is an invention that is capable of capturing dental images without human intervention, and it was invented by the authors of this paper. Adjusting the radiology wave dose is a part of the dentists, radiologists, and dental nurses’ tasks during the radiology photography process. In this paper, an improvement will be added to enable SDDR to set the suitable radiology wave dose according to the density and age of the patients automatically. The separate sensors will be included in the sensors’ package to use the ultrasonic wave to detect the density of the teeth and change the wave dose. It facilitates the process of dental photography in terms of time and enhances the accuracy of choosing the correct wave dose for each patient separately. Since the radiology waves are well known to trigger off other diseases such as cancer, choosing the most suitable wave dose can be helpful to decrease the side effect of that for human health. In other words, it decreases the exposure time for the patients. On the other hand, due to saving time, less energy will be consumed, and saving energy can be beneficial to decrease the environmental impact as well.

Keywords: dental direct digital imaging, environmental impacts, SDDR technology, wave dose

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Authors: Sadia Arshad, Yifa Tang, Dumitru Baleanu

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A fractional order mathematical model is proposed that incorporate CD8+ cells, natural killer cells, cytokines and tumor cells. The tumor cells growth in the absence of an immune response is modeled by logistic law as it was the simplest form for which predictions also agreed with the experimental data. Natural Killer Cells are our first line of defense. NK cells directly kill tumor cells through several mechanisms, including the release of cytoplasmic granules containing perforin and granzyme, expression of tumor necrosis factor (TNF) family members. The effect of the NK cells on the tumor cell population is expressed with the product term. Rational form is used to describe interaction between CD8+ cells and tumor cells. A number of cytokines are produced by NKs, including tumor necrosis factor TNF, IFN, and interleukin (IL-10). Source term for cytokines is modeled by Michaelis-Menten form to indicate the saturated effects of the immune response. Stability of the equilibrium points is discussed for biologically significant values of bifurcation parameters. We studied the treatment of fractional order system by investigating analytical conditions of tumor eradication. Numerical simulations are presented to illustrate the analytical results.

Keywords: cancer model, fractional calculus, numerical simulations, stability analysis

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Authors: Meryam Labyad, Karima Fakiri, Widad Lahmini, Ghizlane Draiss, Mohamed Bouskraoui, Nadia Ouzennou

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Background: Asthma is the most common chronic disease in children, affecting nearly 235 million people worldwide (OMS). In Morocco, asthma is much more common in children than in adults; the prevalence rate in children between 13 and 14 years of age is 20%.1 This pathology is marked by high morbidity, a significant impact on the quality of life and development of children 2 This requires a rigorous management strategy in order to achieve clinical control and reduce any risk to the patient 3 A search for aggravating factors is mandatory if a child has difficulty maintaining good asthma control. The objective of the present study is to describe asthma control during this confinement period in children aged 4 to 11 years followed by a pneumo-paediatric consultation. For children whose asthma is not controlled, a search for associations with promoting factors and adherence to treatment is also among the objectives of the study. Knowing the level of asthma control and influencing factors is a therapeutic priority in order to reduce hospitalizations and emergency care use. Objective: To assess asthma control and determine the factors influencing asthma levels in children with asthma during confinement following the COVID 19 pandemic. Method: Prospective cross-sectional study by questionnaire and structured interview among 66 asthmatic children followed in pediatric pneumology consultation at the CHU MED VI of Marrakech from 13/06/2020 to 13/07/2020, asthma control was assessed by the Childhood Asthma Control Test (C-ACT). Results: 66 children and their parents were included (mean age is 7.5 years), asthma was associated with allergic rhinitis (13.5% of cases), conjunctivitis (9% of cases), eczema (12% of cases), occurrence of infection (10.5% of cases). The period of confinement was marked by a decrease in the number of asthma attacks translated by a decrease in the number of emergency room visits (7.5%) of these asthmatic children, control was well controlled in 71% of the children, this control was significantly associated with good adherence to treatment (p<0.001), no infection (p<0.001) and no conjunctivitis (p=002) or rhinitis (p<0.001). This improvement in asthma control during confinement can be explained by the measures taken in the Kingdom to prevent the spread of COVID 19 (school closures, reduction in industrial activity, fewer means of transport, etc.), leading to a decrease in children's exposure to triggers, which justifies the decrease in the number of children having had an infection, allergic rhinitis or conjunctivitis during this period. In addition, the close monitoring of parents resulted in better therapeutic adherence (42.4% were fully observant). Confinement was positively perceived by 68% of the parents; this perception is significantly associated with the level of asthma control (p<0.001). Conclusion: Maintaining good control can be achieved through improved therapeutic adherence and avoidance of triggers, both of which were achieved during the containment period following the VIDOC pandemic 19.

Keywords: Asthma, control , COVID-19 , children

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Authors: Darya O. Prima, Elena V. Vorontsova, Yuri G. Slizhov, Andrey V. Zibarev

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A broad family of carbocycle-fluorinated aza-heterocycles including 1,3-benzodiazoles (benzimidazoles), 1,2,3-benzotriazoles, 2,1,3-benzothia/selenadiazoles and 1,4-benzodiazines (quinoxalines) was synthesized in the unified way and assessed for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma, a kind of oral cancer) cells. The diazoles, triazoles and selenadiazoles revealed low medium inhibitory concentrations IC50 = 2.2-26.4 µМ and induced the cells’ apoptosis at low concentrations C = 1-25 µМ. For selenadiazoles, cell death dynamics was observed already in the first hours after the treatment. Replacement of one atom F by group Me2N in some cases enlarged apoptotic activity of the compounds towards the Hep2 cells. In contrast, the archetypal (i.e. non-fluorinated) 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole were low toxic (IC50 > 100 µM) and induced apoptosis only at high concentrations. The chlorinated congeners of the heterocycles under discussion were highly toxic towards the Hep2 cells but revealed insignificant ability to induce their apoptosis. Overall, the findings above suggest that fluorinated 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole derivatives can be considered as potential anticancer drugs. For the laryngeal epidermoid carcinoma (for which, according to available statistics, the five-year survival rate remained ~50% during the past 30 years), it is especially important since surgical treatment is seriously complicated here thus encouraging medicament one.

Keywords: Apoptosis, aza-heterocycles, cytotoxicity, fluorinated, Hep2 cells, synthesis

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Authors: Rafat M. Mohareb

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Several D-ring alkylated estrone analogues display exceptionally high affinity for estrogen receptors. In particular, compounds in which an E-ring is formed are known to be involved in the inhibition of steroidogenic enzymes. Such compounds also have an effect on steroid dehydrogenase activity and the ability to inhibit the detrimental action of the steroid sulfatase enzyme. Generally, E-ring extended steroids have been accessed by modification of the C17-ketone in the D-ring by either arylimine or oximino formation, addition of a carbon nucleophile or hydrazone formation. Other approaches have included ketone reduction, silyl enol ether formation or ring-closing metathesis (giving five- or six-membered E-rings). Chemical modification of the steroid D-ring provides a way to alter the functional groups, sizes and stereochemistry of the D-ring, and numerous structure-activity relationships have been established by such synthetic alterations. Steroids bearing heterocycles fused to the D-ring of the steroid nucleus have been of pharmaceutical interest. In the present paper, we report on the efficient synthesis of estrone possessing pyran, pyrimidine and thiazole ring systems. This study focused on the synthesis and biochemical evaluation of newly synthesized heterocyclic compounds which were then subjected through inhibitory evaluations towards human cancer and normal cell lines.

Keywords: estrone, heterocyclization, cytotoxicity, biomedicine

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Authors: Khaled Alabduljabbar

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Background: Benign, isolated, recurrent sixth nerve palsy is very rare in children. Here we report a case of recurrent abducens nerve palsy with no obvious etiology. It is a diagnosis of exclusion. A recurrent benign form of 6th nerve palsy, a rarer still palsy, has been described in the literature, and it is of most likely secondary to inflammatory causes, e.g, following viral and bacterial infections. Purpose: To present a case of 14 months old girl with recurrent attacks of isolated left sixth cranial nerve palsy following upper respiratory tract infection. Observation: The patient presented to opthalmology clinic with sudden onset of inward deviation (esotropia) of the left eye with a compensatory left face turn one week following signs of upper respiratory tract infection. Ophthalmological examination revealed large angle esotropia of the left eye in primary position, with complete limitation of abduction of the left eye, no palpebral fissure changes, and abnormal position of the head (left face turn). Visual acuity was normal, and no significant refractive error on cycloplegic refraction for her age. Fundus examination was normal with no evidence of papilledema. There was no relative afferent pupillary defect (RAPD) and no anisocoria. Past medical history and family history were unremarkable, with no history of convulsion attacks or head trauma. Additional workout include CBC. Erythrocyte sedimentation rate, Urgent magnetic resonance imaging (MRI), and angiography of the brain were performed and demonstrated the absence of intracranial and orbital lesions. Referral to pediatric neurologist was also done and concluded no significant finding. The patient showed improvement of the left sixth cranial nerve palsy and left face turn over a period of two months. Seven months since the first attack, she experienced a recurrent attack of left eye esotropia with left face turn concurrent with URTI. The rest of eye examination was again unremarkable. CT scan and MRI scan of brain and orbit were performed and showed only signs of sinusitis with no intracranial pathology. The palsy resolved spontaneously within two months. A third episode of left 6th nerve palsy occurred 6 months later, whichrecovered over one month. Examination and neuroimagingwere unremarkable. A diagnosis of benign recurrent left 6th cranial nerve palsy was made. Conclusion: Benign sixth cranial nerve palsy is always a diagnosis of exclusion given the more serious and life-threatening alternative causes. It seems to have a good prognosis with only supportive measures. The likelihood of benign 6th cranial nerve palsy to resolve completely and spontaneously is high. Observation for at least 6 months without intervention is advisable.

Keywords: 6th nerve pasy, abducens nerve pasy, recurrent nerve palsy, cranial nerve palsy

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Authors: Chih-Hung Liang, Jung-Jung Chen, Shen-Shih Chiang

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Obesity is defined as abnormal or excessive fat accumulation that presents a risk to health, which are major risk factors for a number of chronic diseases, including diabetes, cardiovascular diseases and cancer. Cordyceps militaris (CM) is a well-known traditional medicine in Asian countries and a rich source of biologically active components. Black rice (Oryza sativa L.) is a special cultivar of rice that contains rich anthocyanins and regarded as a health-promoting food in China and other Eastern. The aim of this study was to investigate the anti-obesity effect of Cordyceps militaris fermented black rice (CB) on HFD-induced BALB/c mice model. The results indicated that administration of low and high dosage of CB powder significantly reduced the body weights (7.38% and 7.78%), body fat ratio (2.37% and 2.78%), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels compared to the HF group (p<0.05). Histopathological analysis showed that the score of fatty liver in HF group (5.0) was significantly higher than CB groups (2.1 and 3.6) (p<0.05). In conclusion, Cordyceps militaris fermented black rice can reduce the body weight via inhibition of the fat accumulation in liver and body and possess the anti-obesity potency.

Keywords: Cordyceps militaris, black rice, obesity, HFD-induced mice

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Authors: Melissa Langevin, Natalie Ward, Colleen Fitzgibbons, Christa Ramsey, Melanie Hogue, Anna Theresa Lobos

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Description: Root Cause Analysis (RCA) is used by health care teams to examine adverse events (AEs) to identify causes which then leads to recommendations for prevention Despite widespread use, RCA has limitations. Best practices have not been established for implementing recommendations or tracking the impact of interventions after AEs. During phase 1 of this study, we used simulation to analyze two fictionalized AEs that occurred in hospitalized paediatric patients to identify and understand how the errors occurred and generated recommendations to mitigate and prevent recurrences. Scenario A involved an error of commission (inpatient drug error), and Scenario B involved detecting an error that already occurred (critical care drug infusion error). Recommendations generated were: improved drug labeling, specialized drug kids, alert signs and clinical checklists. Aim: Use simulation to optimize interventions recommended post critical event analysis prior to implementation in the clinical environment. Methods: Suggested interventions from Phase 1 were designed and tested through scenario simulation in the clinical environment (medicine ward or pediatric intensive care unit). Each scenario was simulated 8 times. Recommendations were tested using different, voluntary teams and each scenario was debriefed to understand why the error was repeated despite interventions and how interventions could be improved. Interventions were modified with subsequent simulations until recommendations were felt to have an optimal effect and data saturation was achieved. Along with concrete suggestions for design and process change, qualitative data pertaining to employee communication and hospital standard work was collected and analyzed. Results: Each scenario had a total of three interventions to test. In, scenario 1, the error was reproduced in the initial two iterations and mitigated following key intervention changes. In scenario 2, the error was identified immediately in all cases where the intervention checklist was utilized properly. Independently of intervention changes and improvements, the simulation was beneficial to identify which of these should be prioritized for implementation and highlighted that even the potential solutions most frequently suggested by participants did not always translate into error prevention in the clinical environment. Conclusion: We conclude that interventions that help to change process (epinephrine kit or mandatory checklist) were more successful at preventing errors than passive interventions (signage, change in memory aids). Given that even the most successful interventions needed modifications and subsequent re-testing, simulation is key to optimizing suggested changes. Simulation is a safe, practice changing modality for institutions to use prior to implementing recommendations from RCA following AE reviews.

Keywords: adverse events, patient safety, pediatrics, root cause analysis, simulation

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Authors: Pei-Wen Lin, Ta-I Yang

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Cancer has been one of the leading causes of human death for centuries. Considerable effort has been devoted to developing new treatments to reduce and control cancers. Magnetic particle hyperthermia and near-infrared photothermal therapy are the promising strategies to treat cancers due to its effectiveness with only mild side effects. This study focused on synthesizing magnetic Ag@Fe3O4 nanoparticles applicable for both of magnetic hyperthermia and near-infrared photothermal therapy. The hydrophilic poly(diallyldimethylammonium chloride) polymer was utilized to prepare superparamagnetic Fe3O4 clusters and to promote silver nanoparticles grown on Fe3O4 surfaces, obtaining Ag@Fe3O4 nanoparticles. The morphology (shape and dimension) of Ag nanoparticles was subsequently tailored using commercial LED lights. Therefore, the resulting Ag@Fe3O4 nanoparticles can absorb specific wavelength of light ranging from 400 nm to 800 nm by adjusting the wavelength of LED lights and the free silver ions in reaction solution. Heating performance tests confirmed that the synthesized Ag@Fe3O4 nanoparticles show appreciable heating capability for both of magnetic particle hyperthermia and near-infrared photothermal therapy. The findings in this study could provide new ideas to design functional materials to treat cancers.

Keywords: light-emitting diode assisted synthesis, magnetic particles, photothermal materials, hyperthermia

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is known to be associated with many clinically important diseases including metabolic syndrome (MetS). Vitamin B₁₂ plays essential roles in fat and protein metabolisms and its cooperation with vitamin B₉ is well-known. The aim of this study is to investigate the possible contributions as well as associations of these micronutrients upon obesity and MetS during childhood. A total of 128 children admitted to Namik Kemal University, Medical Faculty, Department of Pediatrics Outpatient Clinics were included into the scope of this study. The mean age±SEM of 92 morbid obese (MO) children and 36 with MetS were 118.3±3.8 months and 129.5±6.4 months, respectively (p > 0.05). The study was approved by Namık Kemal University, Medical Faculty Ethics Committee. Written informed consent forms were obtained from the parents. Demographic features and anthropometric measurements were recorded. WHO BMI-for age percentiles were used. The values above 99 percentile were defined as MO. Components of MetS [waist circumference (WC), fasting blood glucose (FBG), triacylglycerol (TRG), high density lipoprotein cholesterol (HDL-Chol), systolic pressure (SP), diastolic pressure (DP)] were determined. Routine laboratory tests were performed. Serum vitamin B₁₂ concentrations were measured using electrochemiluminescence immunoassay. Vitamin B₉ was analyzed by an immunoassay analyzer. Values for vitamin B₁₂ < 148 pmol/L, 148-221 pmol/L, > 221 pmol/L were accepted as low, borderline and normal, respectively. Vitamin B₉ levels ≤ 4 mcg/L defined deficiency state. Statistical evaluations were performed by SPSSx Version 16.0. p≤0.05 was accepted as statistical significance level. Statistically higher body mass index (BMI), WC, hip circumference (C) and neck C were calculated in MetS group compared to children with MO. No difference was noted for head C. All MetS components differed between the groups (SP, DP p < 0.001; WC, FBG, TRG p < 0.01; HDL-Chol p < 0.05). Significantly decreased vitamin B₉ and vitamin B₁₂ levels were detected (p < 0.05) in children with MetS. In both groups percentage of folate deficiency was 5.5%. No cases were below < 148 pmol/L. However, in MO group 14.3% and in MetS group 22.2% of the cases were of borderline status. In MO group B₁₂ levels were negatively correlated with BMI, WC, hip C and head C, but not with neck C. WC, hip C, head C and neck C were all negatively correlated with HDL-Chol. None of these correlations were observed in the group of children with MetS. Strong positive correlation between FBG and insulin as well as strong negative correlation between TRG and HDL-Chol detected in MO children were lost in MetS group. Deficiency state end-products of both B₉ and B₁₂ may interfere with the expected profiles of MetS components. In this study, the alterations in MetS components affected vitamin B₁₂ metabolism and also its associations with anthropometric body measurements. Further increases in vitamin B₁₂ and vitamin B₉ deficiency in MetS associated with the increased vitamin B₁₂ as well as vitamin B₉ deficiency metabolites may add to MetS parameters.

Keywords: children, cobalamin, folate, metabolic syndrome, obesity

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Authors: Jack S. Pullman, Daniel Wen, Avinash Sharma, Bert Van Der Werf, Richard Martin

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Background: New Zealand (NZ) melanoma incidence rates are amongst the highest in the world. Previous studies investigating the incidence of melanoma in NZ were performed for the periods 1995 – 1999 and 2000 – 2004 and suggested increasing melanoma incidence rates. Aim: The aim of the study is to provide an up-to-date review of trends in cutaneous melanoma in NZ from the New Zealand Cancer Registry (NZCR) 2010 – 2020. Methods: De-identified data were obtained from the NZCR, and relevant demographic and histopathologic information was extracted. Statistical analyses were conducted to calculate age-standardized incidence rates for invasive melanoma (IM) and melanoma in situ (MIS). Secondary results included Breslow thickness and melanoma subtype analysis. Results: There was a decline in the IM age-standardized incidence rate from 30.4 to 23.9 per 100,000 person-years between 2010 to 2020, alongside an increase in MIS incidence rate from 37.1 to 50.3 per 100,000 person-years. Men had a statistically significant higher IM incidence rate (p <0.001) and Breslow thickness (p <0.001) compared with women. Increased age was associated with a higher incidence of IM, presentation with melanoma of greater Breslow thickness and more advanced T stage. Conclusion: The incidence of IM in NZ has decreased in the last decade and was associated with an increase in MIS incidence over the same period. This can be explained due to earlier detection, dermoscopy, the maturity of prevention campaigns and/or a change in skin protection behavior.

Keywords: melanoma, incidence, epidemiology, New Zealand

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Authors: Daruliza Kernain, Shaharum Shamsuddin, See Too Wei Cun

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CTCF is a unique, highly conserved and ubiquitously expressed 11 zinc finger (ZF) transcriptional factor with multiple target sites. It is able to bind to various target sequences to perform different regulatory roles including promoter activation or repression, creating hormone-responsive gene silencing element, and functional block of enhancer-promoter interactions. The binding of CTCF to the essential binding site is through the combination of different ZF domain. On the other hand, BORIS for brother of the regulator of imprinted sites, which expressed only in the testis and certain cancer cell line is homology to CTCF 11 ZF domains. Since both transcriptional factors share the same ZF domains hence there is a possibility for both to bind to the same target sequences. In this study, the interaction of these two proteins to multi-functional Y-box DNA/RNA-binding factor, YB-1 was determined. The protein-protein interaction between CTCF/YB-1 and BORIS/YB-1 were discovered by Co-immuno-precipitation (CO-IP) technique through reciprocal experiment from RGBM total cell lysate. The results showed that both CTCF and BORIS were able to interact with YB-1 in Glioma RGBM cell line. To the best of our knowledge, this is the first findings demonstrating the ability of BORIS and YB-1 to form a complex in vivo.

Keywords: immunoprecipitation, CTCF/BORIS/YB-1, transcription factor, molecular medicine

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Authors: Fern Baedyananda, Arkom Chaiwongkot, Somchai Niruthisard, Nakarin Kitkumthorn, Parvapan Bhattarakosol

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High-risk human papillomavirus (HPV) infections cause transformation of the host cells by down-regulating and inhibiting host regulatory proteins such as p53 and pRb by overexpressing the viral oncoproteins E6 and E7. However, the E1 protein which is the only enzyme encoded by HPV has also been shown to cause DNA instability leading to the integration of the virus into the host genome and triggering carcinogenic events. A 63bp duplication in the E1 helicase region has been detected in European patients. However, the clinical prognosis of these patients is still controversial. This study was performed to determine the presence of the HPV-16 E1 63bp duplication in patient cervical samples in Thai women and determine the sequence of the variant in the Thai population. Detection of the HPV-16 E1 duplication in the helicase region was performed in 90 patient cell samples across normal, cervical intraepithelial neoplasia I-III, and squamous cervical carcinoma stages by PCR. The PCR products were purified and sequenced to determine the presence of duplication variants.The variant form was found in 10% of all CIN 1 patients. In this study, the presence of the 63 bp duplication variant in the Thai population was found to be present and was further characterized. Interestingly, all samples that exhibited the variant form of HPV-16 E1 were classified as CIN I. Presence of the variant, constricted to mild dysplasia signifies the importance of HPV-16 E1 in carcinogenesis.

Keywords: carcinogenesis, cervical cancer, human papillomavirus, HPV-16 E1

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