Search results for: invasive breast carcinoma (IBC)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1512

Search results for: invasive breast carcinoma (IBC)

252 Impact of Hormone Replacement Therapy on Body Composition Analysis of Women during Perimenopause: A Framework for Action

Authors: Varsha Chorsiya, Pooja Aneja, Dhananjay Kaushik, Abhinav Yadav

Abstract:

Intoduction: Women’s Health Initiatives (WHI) focuses on defining the risks and benefits of strategies that could potentially reduce the incidence of obesity, heart disease, breast cancer and colorectal cancer, and fractures in menopause women. The utility of the present research work determines to find the role of Hormone Replacement Therapy (HRT) in changing the different component of body composition during perimenopause period. Methods: A comparative cross-sectional study included 30 subjects, aged between 40 and 50 years which were assigned into 2 groups i.e. 15 subjects in HRT (Group A) and 15 subjects in non-HRT (Group B). The subjects were taken from the hospitals and clinics of Faridabad undergoing HRT in supervision of the consultant gynecologist. The informed consents were signed before including the participants in the study. The body composition and lipid profile were evaluated for all the subjects. Result and Discussion: The BMI, body density, percent body fats and fat mass in both groups showed statistically significant differences i.e. p < 0.05. Our study did not reveal any statistically significant difference between non-HRT and HRT for lipid profile composition of HDL, LDL, VLDL, ratio, triglycerides and total cholesterol although these indicators (LDL, VLDL, ratio, triglycerides and total cholesterol) showed difference clinically with a higher mean values for non-HRT as compared to HRT group. The mean value for HDL was higher for HRT group in contrast to non-HRT group. The result clearly showed that HRT group has a good lipid profile composition. Conclusion: In conclusion, our data show that HRT has statistically significant role in determining BMI, fat percent mass and fat mass. The lipid profile including LDL, HDL, VLDL, ratio, triglycerides and total cholesterol found to be clinically better in HRT group as compared to the non-HRT group. The rationale for non-significant lipid profile probably lie in the fact that hormonal changes need a particular time period and might become significant in post-menopausal period.

Keywords: body composition, hormone replacement therapy, perimenopause, women health

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251 Magnetic Bio-Nano-Fluids for Hyperthermia

Authors: Z. Kolacinski, L. Szymanski. G. Raniszewski, D. Koza, L. Pietrzak

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Magnetic Bio-Nano-Fluid (BNF) can be composed of a buffer fluid such as plasma and magnetic nanoparticles such as iron, nickel, cobalt and their oxides. However iron is one of the best elements for magnetization by electromagnetic radiation. It can be used as a tool for medical diagnosis and treatment. Radio frequency (RF) radiation is able to heat iron nanoparticles due to magnetic hysteresis. Electromagnetic heating of iron nanoparticles and ferro-fluids BNF can be successfully used for non-invasive thermal ablation of cancer cells. Moreover iron atoms can be carried by carbon nanotubes (CNTs) if iron is used as catalyst for CNTs synthesis. Then CNTs became the iron containers and they screen the iron content against oxidation. We will present a method of CNTs addressing to the required cells. For thermal ablation of cancer cells we use radio frequencies for which the interaction with human body should be limited to minimum. Generally, the application of RF energy fields for medical treatment is justified by deep tissue penetration. The highly iron doped CNTs as the carriers creating magnetic fluid will be presented. An excessive catalyst injection method using electrical furnace and microwave plasma reactor will be presented. This way it is possible to grow the Fe filled CNTs on a moving surface in continuous synthesis process. This also allows producing uniform carpet of the Fe filled CNTs carriers. For the experimental work targeted to cell ablation we used RF generator to measure the increase in temperature for some samples like: solution of Fe2O3 in BNF which can be plasma-like buffer, solutions of pure iron of different concentrations in plasma-like buffer and in buffer used for a cell culture, solutions of carbon nanotubes (MWCNTs) of different concentrations in plasma-like buffer and in buffer used for a cell culture. Then the targeted therapies which can be effective if the carriers are able to distinguish the difference between cancerous and healthy cell’s physiology are considered. We have developed an approach based on ligand-receptor or antibody-antigen interactions for the case of colon cancer.

Keywords: cancer treatment, carbon nano tubes, drag delivery, hyperthermia, iron

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250 CSPG4 Molecular Target in Canine Melanoma, Osteosarcoma and Mammary Tumors for Novel Therapeutic Strategies

Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

Abstract:

Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

Procedia PDF Downloads 147
249 Comparison of Maternal and Perinatal Outcomes of Obstetric Population Diagnosed with Covid-19 in Reference to Influenza A/H1N1: A Systematic Review and Meta-Analysis

Authors: Maria Vargas Hernandez, Jose Rojas Suarez, Carmelo Dueñas Castell, Sandra Contreras, Camilo Bello, Diana Borre, Walter Anichiarico, Harold Vasquez, Eduard Perez, Jose Santacruz

Abstract:

In the last two decades, there have been outbreaks of emerging infectious diseases, with an impact on both the general population and the obstetric population. These infections, which affect the general population, pose a high risk for adverse maternal and perinatal outcomes, taking into account that physiological and immunological changes that occur during pregnancy can increase their risk or severity. Among these, the pandemics of viral infections, Influenza A/H1N1 and SARS-CoV-2/COVID-19, stand out. In 2009, Influenza A/H1N1 infection (H1N1 2009pdm) affected approximately 3,110 obstetric patients, with data reported from 29 countries, including 1,625 (52.3%) cases that were hospitalized, 378 (23.3%) admissions to ICU and 130 (8%) deaths; and since the end of 2019, the Severe Acute Respiratory Syndrome - 2 (SARS-CoV-2) has been identified, causing the COVID-19 pandemic, with global mortality that is around 2-4% for the general population, and higher mortality in patients requiring admission to the intensive care unit. Its impact on the obstetric population is still unknown. Objectives: To evaluate the impact on maternal and perinatal outcomes of COVID-19 infection in reference to influenza A/H1N1 infection in the obstetric population. Methodology: Systematic review of the literature and meta-analysis. Results: Mortality from maternal infection with influenza A/H1N1 appears to be higher (8%) than mortality due to maternal infection with COVID-19 (3%). The rates of ICU admission, hospitalization, the requirement for invasive mechanical ventilation, and fetal death also appear to be higher in the maternal population with A/H1N1 infection, in reference to the maternal population with COVID-19 infection. Within perinatal outcomes, the admission to the neonatal ICU appears to be higher in the infants born to mothers with COVID-19 infection (28% vs. 15% for COVID-19 and A/H1N1, respectively). Conclusion: A/H1N1 infection in the obstetric population seems to be associated with a higher proportion of adverse outcomes in relation to COVID-19 infection. The actual impact of maternal influenza A/H1N1 infection on perinatal outcomes is unknown. More COVID-19 studies are needed to understand the impact of maternal infection on perinatal outcomes in this population.

Keywords: A/H1N1, COVID-19, maternal outcomes, perinatal outcomes

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248 Immunomodulatory Role of Heat Killed Mycobacterium indicus pranii against Cervical Cancer

Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

Abstract:

Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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247 The Role of Disturbed Dry Afromontane Forest of Ethiopia for Biodiversity Conservation and Carbon Storage

Authors: Mindaye Teshome, Nesibu Yahya, Carlos Moreira Miquelino Eleto Torres, Pedro Manuel Villaa, Mehari Alebachew

Abstract:

Arbagugu forest is one of the remnant dry Afromontane forests under severe anthropogenic disturbances in central Ethiopia. Despite this fact, up-to-date information is lacking about the status of the forest and its role in climate change mitigation. In this study, we evaluated the woody species composition, structure, biomass, and carbon stock in this forest. We employed a systematic random sampling design and established fifty-three sample plots (20 × 100 m) to collect the vegetation data. A total of 37 woody species belonging to 25 families were recorded. The density of seedlings, saplings, and matured trees were 1174, 101, and 84 stems ha-1, respectively. The total basal area of trees with DBH (diameter at breast height) ≥ 2 cm was 21.3 m2 ha-1. The characteristic trees of dry Afromontane Forest such as Podocarpus falcatus, Juniperus procera, and Olea europaea subsp. cuspidata exhibited a fair regeneration status. On the contrary, the least abundant species Lepidotrichilia volkensii, Canthium oligocarpum, Dovyalis verrucosa, Calpurnia aurea, and Maesa lanceolata exhibited good regeneration status. Some tree species such as Polyscias fulva, Schefflera abyssinica, Erythrina brucei, and Apodytes dimidiata lack regeneration. The total carbon stored in the forest ranged between 6.3 Mg C ha-1 and 835.6 Mg C ha-1. This value is equivalent to 639.6 Mg C ha-1. The forest had a very low number of woody species composition and diversity. The regeneration study also revealed that a significant number of tree species had unsatisfactory regeneration status. Besides, the forest had a lower carbon stock density compared with other dry Afromontane forests. This implies the urgent need for forest conservation and restoration activities by the local government, conservation practitioners, and other concerned bodies to maintain the forest and sustain the various ecosystem goods and services provided by the Arbagugu forest.

Keywords: aboveground biomass, forest regeneration, climate change, biodiversity conservation, restoration

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246 Scenario of Some Minerals and Impact of Promoter Hypermethylation of DAP-K Gene in Gastric Carcinoma Patients of Kashmir Valley

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

Abstract:

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

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

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245 The Incidence of Cardiac Arrhythmias Using Trans-Telephonic, Portable Electrocardiography Recorder, in Out-Patients Faculty of Medicine Ramathibodi Hospital

Authors: Urasri Imsomboon, Sopita Areerob, Kanchaporn Kongchauy, Tuchapong Ngarmukos

Abstract:

Objective: The Trans-telephonic Electrocardiography (ECG) monitoring is used to diagnose of infrequent cardiac arrhythmias and improve outcome of early detection and treatment on suspected cardiac patients. The objectives of this study were to explore incidence of cardiac arrhythmia using Trans-Telephonic and to explore time to first symptomatic episode and documented cardiac arrhythmia in outpatients. Methods: Descriptive research study was conducted between February 1, 2016, and December 31, 2016. A total of 117 patients who visited outpatient clinic were purposively selected. Research instruments in this study were the personal data questionnaire and the record form of incidence of cardiac arrhythmias using Trans-Telephonic ECG recorder. Results: A total of 117 patients aged between 15-92 years old (mean age 52.7 ±17.1 years), majority of studied sample was women (64.1%). The results revealed that 387 ECGs (Average 2.88 ECGs/person, SD = 3.55, Range 0 – 21) were sent to Cardiac Monitoring Center at Coronary Care Unit. Of these, normal sinus rhythm was found mostly 46%. Top 5 of cardiac arrhythmias were documented at the time of symptoms: sinus tachycardia 43.5%, premature atrial contraction 17.7%, premature ventricular contraction 14.3%, sinus bradycardia 11.5% and atrial fibrillation 8.6%. Presenting symptom were tachycardia 94%, palpitation 83.8%, dyspnea 51.3%, chest pain 19.6%, and syncope 14.5%. Mostly activities during symptom were no activity 64.8%, sleep 55.6% and work 25.6%.The mean time until the first symptomatic episode occurred on average after 6.88 ± 7.72 days (median 3 days). The first documented cardiac arrhythmia occurred on average after 9 ± 7.92 days (median 7 day). The treatments after patients known actual cardiac arrhythmias were observe themselves 68%, continue same medications 15%, got further investigations (7 patients), and corrected causes of cardiac arrhythmias via invasive cardiac procedures (5 patients). Conclusion: Trans-telephonic: portable ECGs recorder is effective in the diagnosis of suspected symptomatic cardiac arrhythmias in outpatient clinic.

Keywords: cardiac arrhythmias, diagnosis, outpatient clinic, trans-telephonic: portable ECG recorder

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244 Oncolytic H-1 Parvovirus Entry in Cancer Cells through Clathrin-Mediated Endocytosis

Authors: T. Ferreira, A. Kulkarni, C. Bretscher, K. Richter, M. Ehrlich, A. Marchini

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H-1 protoparvovirus (H-1PV) is a virus with inherent oncolytic and oncosuppressive activities while remaining non-pathogenic in humans. H-1PV was the first oncolytic parvovirus to undergo clinical testing. Results from trials in patients with glioblastoma or pancreatic carcinoma showed an excellent safety profile and first signs of efficacy. H-1PV infection is vastly dependent on cellular factors, from cell attachment and entry to viral replication and egress. Hence, we believe that the characterisation of the parvovirus life cycle would ultimately help further improve H-1PV clinical outcome. In the present study, we explored the entry pathway of H-1PV in cervical HeLa and glioma NCH125 cancer cell lines. Electron and confocal microscopy showed viral particles associated with clathrin-coated pits and vesicles, providing the first evidence that H-1PV cell entry occurs through clathrin-mediated endocytosis. Accordingly, we observed that by blocking clathrin-mediated endocytosis with hypertonic sucrose, chlorpromazine, or pitstop 2, H-1PV transduction was markedly decreased. Accordingly, siRNA-mediated knockdown of AP2M1, which retains a crucial role in clathrin-mediated endocytosis, verified the reliance of H-1PV on this route to enter HeLa and NCH125 cancer cells. By contrast, we found no evidence of viral entry through caveolae-mediated endocytosis. Indeed, pre-treatment of cells with nystatin or methyl-β-cyclodextrin, both inhibitors of caveolae-mediated endocytosis, did not affect viral transduction levels. Unexpectedly, siRNA-mediated knockdown of caveolin-1, the main driver of caveolae-mediated endocytosis, increased H-1PV transduction, suggesting caveolin-1 is a negative modulator of H-1PV infection. We also show that H-1PV entry is dependent on dynamin, a protein responsible for mediating the scission of vesicle neck and promoting further internalisation. Furthermore, since dynamin inhibition almost completely abolished H-1PV infection, makes it unlikely that H-1PV uses macropinocytosis as an alternative pathway to enter cells. After viral internalisation, H-1PV passes through early to late endosomes as observed by confocal microscopy. Inside these endocytic compartments, the acidic environment proved to be crucial for a productive infection. Inhibition of acidification of pH dramatically reduced H-1PV transduction. Besides, a fraction of H-1PV particles was observed inside LAMP1-positive lysosomes, most likely following a non-infectious route. To the author's best knowledge, this is the first study to characterise the cell entry pathways of H-1PV. Along these lines, this work will further contribute to understand H-1PV oncolytic properties as well as to improve its clinical potential in cancer virotherapy.

Keywords: clathrin-mediated endocytosis, H-1 parvovirus, oncolytic virus, virus entry

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243 Polymeric Micelles Based on Block Copolymer α-Tocopherol Succinate-g-Carboxymethyl Chitosan for Tamoxifen Delivery

Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

Abstract:

Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

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242 Dietary Vitamin D Intake and the Bladder Cancer Risk: A Pooled Analysis of Prospective Cohort Studies

Authors: Iris W. A. Boot, Anke Wesselius, Maurice P. Zeegers

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Diet may play an essential role in the aetiology of bladder cancer (BC). Vitamin D is involved in various biological functions which have the potential to prevent BC development. Besides, vitamin D also influences the uptake of calcium and phosphorus , thereby possibly indirectly influencing the risk of BC. The aim of the present study was to investigate the relation between vitamin D intake and BC risk. Individual dietary data were pooled from three cohort studies. Food item intake was converted to daily intakes of vitamin D, calcium and phosphorus. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) were obtained using Cox-regression models. Analyses were adjusted for gender, age and smoking status (Model 1), and additionally for the food groups fruit, vegetables and meat (Model 2). Dose–response relationships (Model 1) were examined using a nonparametric test for trend. In total, 2,871 cases and 522,364 non-cases were included in the analyses. The present study showed an overall increased BC risk for high dietary vitamin D intake (HR: 1.14, 95% CI: 1.03-1.26). A similar increase BC risk with high vitamin D intake was observed among women and for the non-muscle invasive BC subtype, (HR: 1.41, 95% CI: 1.15-1.72, HR: 1.13, 95% CI: 1.01-1.27, respectively). High calcium intake decreased the BC risk among women (HR: 0.81, 95% CI: 0.67-0.97). A combined inverse effect on BC risk was observed for low vitamin D intake and high calcium intake (HR: 0.67, 95% CI: 0.48-0.93), while a positive effect was observed for high vitamin D intake in combination with low, moderate and high phosphorus (HR: 1.31, 95% CI: 1.09-1.59, HR: 1.17, 95% CI: 1.01-1.36, HR: 1.16, 95% CI: 1.03-1.31, respectively). Combining all nutrients showed a decreased BC risk for low vitamin D intake, high calcium and moderate phosphor intake (HR: 0.37, 95% CI: 0.18-0.75), and an increased BC risk for moderate intake of all the nutrients (HR: 1.18, 95% CI: 1.02-1.38), for high vitamin D and low calcium and phosphor intake (HR: 1.28, 95% CI: 1.01-1.62), and for moderate vitamin D and calcium and high phosphorus intake (HR: 1.27, 95% CI: 1.01-1.59). No significant dose-response analyses were observed. The findings of this study show an increased BC risk for high dietary vitamin D intake and a decreased risk for high calcium intake. Besides, the study highlights the importance of examining the effect of a nutrient in combination with complementary nutrients for risk assessment. Future research should focus on nutrients in a wider context and in nutritional patterns.

Keywords: bladder cancer, nutritional oncology, pooled cohort analysis, vitamin D

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241 Pattern Recognition Approach Based on Metabolite Profiling Using In vitro Cancer Cell Line

Authors: Amanina Iymia Jeffree, Reena Thriumani, Mohammad Iqbal Omar, Ammar Zakaria, Yumi Zuhanis Has-Yun Hashim, Ali Yeon Md Shakaff

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Metabolite profiling is a strategy to be approached in the pattern recognition method focused on three types of cancer cell line that driving the most to death specifically lung, breast, and colon cancer. The purpose of this study was to discriminate the VOCs pattern among cancerous and control group based on metabolite profiling. The sampling was executed utilizing the cell culture technique. All culture flasks were incubated till 72 hours and data collection started after 24 hours. Every running sample took 24 minutes to be completed accordingly. The comparative metabolite patterns were identified by the implementation of headspace-solid phase micro-extraction (HS-SPME) sampling coupled with gas chromatography-mass spectrometry (GCMS). The optimizations of the main experimental variables such as oven temperature and time were evaluated by response surface methodology (RSM) to get the optimal condition. Volatiles were acknowledged through the National Institute of Standards and Technology (NIST) mass spectral database and retention time libraries. To improve the reliability of significance, it is of crucial importance to eliminate background noise which data from 3rd minutes to 17th minutes were selected for statistical analysis. Targeted metabolites, of which were annotated as known compounds with the peak area greater than 0.5 percent were highlighted and subsequently treated statistically. Volatiles produced contain hundreds to thousands of compounds; therefore, it will be optimized by chemometric analysis, such as principal component analysis (PCA) as a preliminary analysis before subjected to a pattern classifier for identification of VOC samples. The volatile organic compound profiling has shown to be significantly distinguished among cancerous and control group based on metabolite profiling.

Keywords: in vitro cancer cell line, metabolite profiling, pattern recognition, volatile organic compounds

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240 Growth and Bone Health in Children following Liver Transplantation

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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239 On-Farm Evaluation of Fast and Slow Growing Genotypes for Organic and Pasture Poultry Production Systems

Authors: Komala Arsi, Terrel Spencer, Casey M. Owens, Dan J. Donoghue, Ann M. Donoghue

Abstract:

Organic poultry production is becoming increasingly popular in the United States with approximately 17% increase in the sales of organic meat and poultry in 2016. As per the National Organic Program (NOP), organic poultry production system should operate according to specific standards, including access to outdoors. In the United States, organic poultry farmers are raising both fast growing and slow growing genotypes for alternative productive systems. Even though heritage breed birds grow much slower compared to commercial breeds, many free range producers believe that they are better suited for outdoor production systems. We conducted an on-farm trial on a working pasture poultry farm to compare the performance and meat quality characteristics of a slow-growing heritage breed (Freedom Rangers, FR), and two commonly used fast growing types of chickens (Cornish cross, CC and Naked Neck, NN), raised on pasture, in side by side pens segregated by breed (n=70/breed). CC and NN group birds were reared for eight weeks whereas FR group birds were reared for 10 weeks and all the birds were commercially processed. By the end of the rearing period, the final body weight of FR group birds was significantly lower than both the fast growing genotypes (CC and NN). Both CC and NN birds showed significantly higher live weight, carcass weight as well as fillet, tender and leg yield (P < 0.05). There was no difference in the wing and rack yield among the different groups. Color of the meat was measured using CEILAB method and expressed as lightness (L), redness (a*) and yellowness (b*). The breast meat from FR birds was much redder (higher a* values) and less yellow (lesser b* values) compared to both the fast growing type of chickens (P < 0.05). Overall, fast growing genotypes produced higher carcass weight and meat yield compared to slow growing genotypes and appear to be an economical option for alternative production systems.

Keywords: fast growing chickens, meat quality, pasture, slow growing chickens

Procedia PDF Downloads 359
238 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

Abstract:

Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

Procedia PDF Downloads 61
237 Comparative in vitro Anticancer Activity of Two Siddha Formulations: Neeradi Muthu Vallathymezugu and Thamira Kattu Chendooram

Authors: Vasudha Devi, Arul Amuthan, K. Narayanan, Praveen KS, Venkata Rao J

Abstract:

Background: Siddha Medicine is one of the Indian traditional medical systems, in which the cancer disease is mentioned as 'putrunoi' which literally means the disease of growth like termite mound. There are number of formulations available for the treatment of cancer disease. Neeradi muthu vallathymezugu (NMV) and thamira kattu chendooram (TKC) are two drugs commonly prescribed by Siddha physicians. These drugs have been clinically reported to be safe and effective when given orally. Though these formulations are in practice for centuries, no efforts have been made to standardize them and explore their anti-cancer potential systematically. Objective: To compare the cytotoxic activity of NMV and TKC with doxorubicin using cancer cell lines. Materials and methods: For this study, ethanol extract of NMV was taken, whereas TKC was used as such. In vitro cytotoxic activity was evaluated by sulphorhodamine (SRB) assay against human hepatic cancer cells (HepG2), human breast cancer cells (MCF-7) and human cervical cancer cells [KeLa]. Doxorubicin was used as the standard. The SRB assay is based on the ability of cellular proteins to bind with sulphorhodamine-B. The number of live cells in drug treated cell lines directly affects the color formation in the assay, which is estimated calorimetrically by measuring the absorbance at 540 nm to calculate the cytotoxicity (inhibitory concentration - IC50 value) of the drug. Results: The IC50values of NMV, TKC and doxorubicin against HepG2 were 3.08 µg/ml, 20.21 µg/ml and 1.21µg/ml respectively. In MCF-7, it was 11.75 µg/ml, 17.67 µg/ml and 2.8µg/ml. In HeLa, the values were 24.76 µg/ml, 73.35 µg/ml and 1.12µg/ml. Conclusions: The study proves the possible anti-cancer potential of these two formulations. Compared to TKC, NMV showed good cytotoxic effect even at low dose. Human hepatic cancer cells responded well even at very low dose, when compared to other cancer cells. Though, cytotoxic potential of these compounds was found to be less compared to doxorubicin, the isolated lead compound may have the potential to be used as an anticancer drug clinically.

Keywords: Neeradi muthu vallathymezugu (Hydnocarpus laurifolia), thamira kattu chendooram, cytotoxicity, in-vitro, Siddha Medicine

Procedia PDF Downloads 431
236 Typification and Determination of Antibiotic Resistance Rates of Stenotrophomonas Maltophilia Strains Isolated from Intensive Care Unit Patients in a University Practice and Research Hospital

Authors: Recep Kesli, Gulsah Asik, Cengiz Demir, Onur Turkyilmaz

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Objective: Stenotrophomonas maltophilia (S. maltophilia) has recently emerged as an important nosocomial microorganism. Treatment of invasive infections caused by this organism is problematic because this microorganism is usually resistant to a wide range of commonly used antimicrobials. We aimed to evaluate clinical isolates of S. maltophilia in respect to sampling sites and antimicrobial resistant. Method: During a two years period (October 2013 and September 2015) eighteen samples collected from the intensive care unit (ICU) patients hospitalized in Afyon Kocatepe University, ANS Practice and Research Hospital. Identification of the bacteria was determined by conventional methods and automated identification system-VITEK 2 (bio-Mérieux, Marcy l’toile, France). Antibacterial resistance tests were performed by Kirby Bauer disc (Oxoid, England) diffusion method following the recommendations of CLSI. Results: Eighteen S. maltophilia strains were identified as the causative agents of different infections. The main type of infection was lower respiratory tract infection (83,4 %); three patients (16,6 %) had bloodstream infection. While, none of the 18 S. maltophilia strains were found to be resistant against to trimethoprim sulfametaxasole (TMP-SXT) and levofloxacine, eight strains 66.6 % were found to be resistant against ceftazidim. Conclusion: The isolation of S.maltophilia starains resistant to TMP-SXT is vital. In order to prevent or minimize infections due to S. maltophilia such precuations should be utilized: Avoidance of inappropriate antibiotic use, prolonged implementation of foreign devices, reinforcement of hand hygiene practices and the application of appropriate infection control practices. Microbiology laboratories also may play important roles in controlling S. maltophilia infections by monitoring the prevalence, continuously, the provision of local antibiotic resistance paterns data and the performance of synergistic studies also may help to guide appropirate antimicrobial therapy choices.

Keywords: Stenotrophomonas maltophilia, trimethoprim-sulfamethoxazole, antimicrobial resistance, Stenotrophomonas spp.

Procedia PDF Downloads 225
235 Anticancer Effect of Doxorubicin Using Injectable Hydrogel

Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

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Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

Procedia PDF Downloads 378
234 Electrochemical Impedance Spectroscopy Based Label-Free Detection of TSG101 by Electric Field Lysis of Immobilized Exosomes from Human Serum

Authors: Nusrat Praween, Krishna Thej Pammi Guru, Palash Kumar Basu

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Designing non-invasive biosensors for cancer diagnosis is essential for developing an affordable and specific tool to measure cancer-related exosome biomarkers. Exosomes, released by healthy as well as cancer cells, contain valuable information about the biomarkers of various diseases, including cancer. Despite the availability of various isolation techniques, ultracentrifugation is the standard technique that is being employed. Post isolation, exosomes are traditionally exposed to detergents for extracting their proteins, which can often lead to protein degradation. Further to this, it is very essential to develop a sensing platform for the quantification of clinically relevant proteins in a wider range to ensure practicality. In this study, exosomes were immobilized on the Au Screen Printed Electrode (SPE) using EDC/NHS chemistry to facilitate binding. After immobilizing the exosomes on the screen-printed electrode (SPE), we investigated the impact of the electric field by applying various voltages to induce exosome lysis and release their contents. The lysed solution was used for sensing TSG101, a crucial biomarker associated with various cancers, using both faradaic and non-faradaic electrochemical impedance spectroscopy (EIS) methods. The results of non-faradaic and faradaic EIS were comparable and showed good consistency, indicating that non-faradaic sensing can be a reliable alternative. Hence, the non-faradaic sensing technique was used for label-free quantification of the TSG101 biomarker. The results were validated using ELISA. Our electrochemical immunosensor demonstrated a consistent response of TSG101 from 125 pg/mL to 8000 pg/mL, with a detection limit of 0.125 pg/mL at room temperature. Additionally, since non-faradic sensing is label-free, the ease of usage and cost of the final sensor developed can be reduced. The proposed immunosensor is capable of detecting the TSG101 protein at low levels in healthy serum with good sensitivity and specificity, making it a promising platform for biomarker detection.

Keywords: biosensor, exosomes isolation on SPE, electric field lysis of exosome, EIS sensing of TSG101

Procedia PDF Downloads 16
233 Predictors of Clinical Failure After Endoscopic Lumbar Spine Surgery During the Initial Learning Curve

Authors: Daniel Scherman, Daniel Madani, Shanu Gambhir, Marcus Ling Zhixing, Yingda Li

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Objective: This study aims to identify clinical factors that may predict failed endoscopic lumbar spine surgery to guide surgeons with patient selection during the initial learning curve. Methods: This is an Australasian prospective analysis of the first 105 patients to undergo lumbar endoscopic spine decompression by 3 surgeons. Modified MacNab outcomes, Oswestry Disability Index (ODI) and Visual Analogue Score (VAS) scores were utilized to evaluate clinical outcomes at 6 months postoperatively. Descriptive statistics and Anova t-tests were performed to measure statistically significant (p<0.05) associations between variables using GraphPad Prism v10. Results: Patients undergoing endoscopic lumbar surgery via an interlaminar or transforaminal approach have overall good/excellent modified MacNab outcomes and a significant reduction in post-operative VAS and ODI scores. Regardless of the anatomical location of disc herniations, good/excellent modified MacNab outcomes and significant reductions in VAS and ODI were reported post-operatively; however, not in patients with calcified disc herniations. Patients with central and foraminal stenosis overall reported poor/fair modified MacNab outcomes. However, there were significant reductions in VAS and ODI scores post-operatively. Patients with subarticular stenosis or an associated spondylolisthesis reported good/excellent modified MacNab outcomes and significant reductions in VAS and ODI scores post-operatively. Patients with disc herniation and concurrent degenerative stenosis had generally poor/fair modified MacNab outcomes. Conclusion: The outcomes of endoscopic spine surgery are encouraging, with a low complication and reoperation rate. However, patients with calcified disc herniations, central canal stenosis or a disc herniation with concurrent degenerative stenosis present challenges during the initial learning curve and may benefit from traditional open or other minimally invasive techniques.

Keywords: complications, lumbar disc herniation, lumbar endoscopic spine surgery, predictors of failed endoscopic spine surgery

Procedia PDF Downloads 106
232 Application and Utility of the Rale Score for Assessment of Clinical Severity in Covid-19 Patients

Authors: Naridchaya Aberdour, Joanna Kao, Anne Miller, Timothy Shore, Richard Maher, Zhixin Liu

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Background: COVID-19 has and continues to be a strain on healthcare globally, with the number of patients requiring hospitalization exceeding the level of medical support available in many countries. As chest x-rays are the primary respiratory radiological investigation, the Radiological Assessment of Lung Edema (RALE) score was used to quantify the extent of pulmonary infection on baseline imaging. Assessment of RALE score's reproducibility and associations with clinical outcome parameters were then evaluated to determine implications for patient management and prognosis. Methods: A retrospective study was performed with the inclusion of patients testing positive for COVID-19 on nasopharyngeal swab within a single Local Health District in Sydney, Australia and baseline x-ray imaging acquired between January to June 2020. Two independent Radiologists viewed the studies and calculated the RALE scores. Clinical outcome parameters were collected and statistical analysis was performed to assess RALE score reproducibility and possible associations with clinical outcomes. Results: A total of 78 patients met inclusion criteria with the age range of 4 to 91 years old. RALE score concordance between the two independent Radiologists was excellent (interclass correlation coefficient = 0.93, 95% CI = 0.88-0.95, p<0.005). Binomial logistics regression identified a positive correlation with hospital admission (1.87 OR, 95% CI= 1.3-2.6, p<0.005), oxygen requirement (1.48 OR, 95% CI= 1.2-1.8, p<0.005) and invasive ventilation (1.2 OR, 95% CI= 1.0-1.3, p<0.005) for each 1-point increase in RALE score. For each one year increased in age, there was a negative correlation with recovery (0.05 OR, 95% CI= 0.92-1.0, p<0.01). RALE scores above three were positively associated with hospitalization (Youden Index 0.61, sensitivity 0.73, specificity 0.89) and above six were positively associated with ICU admission (Youden Index 0.67, sensitivity 0.91, specificity 0.78). Conclusion: The RALE score can be used as a surrogate to quantify the extent of COVID-19 infection and has an excellent inter-observer agreement. The RALE score could be used to prognosticate and identify patients at high risk of deterioration. Threshold values may also be applied to predict the likelihood of hospital and ICU admission.

Keywords: chest radiography, coronavirus, COVID-19, RALE score

Procedia PDF Downloads 157
231 Noninvasive Neurally Adjusted Ventilation versus Nasal Continuous or Intermittent Positive Airway Pressure for Preterm Infants: A Systematic Review and Meta-Analysis

Authors: Mohammed S. Bhader, Abdullah A. Ghaddaf, Anas Alamoudi, Amal Abualola, Renad Kalantan, Noura Alkhulaifi, Ibrahim Halawani, Mohammed Alhindi

Abstract:

Background: Noninvasive neurally adjusted ventilatory assist (NAVA) is a relatively new mode of noninvasive ventilation with promising clinical and patient-ventilator outcomes for preterm infants. The aim of this systematic review was to compare NAVA to nasal continuous or positive airway pressure (NCPAP) or intermittent positive airway pressure (NIPP) for preterm infants. Methods: We searched the online databases Medline, Embase, and CENTRAL. We included randomized controlled trials (RCTs) that compared NAVA to NCPAP or NIPP for preterm infants < 37 weeks gestational age. We sought to evaluate the following outcomes: noninvasive intubation failure rate, desaturation rate, the fraction of inspired oxygen (FiO2), and length of stay in the neonatal intensive care unit (NICU). We used the mean difference (MD) to represent continuous outcomes, while the odds ratio (OR) was used to represent dichotomous outcomes. Results: A total of 11 RCTs that enrolled 429 preterm infants were deemed eligible. NAVA showed similar clinical outcomes to NCPAP or NIPP with respect to noninvasive intubation failure (RR for NAVA versus NCPAP: 0.82, 95% confidence interval (CI): 0.49 to 1.37), desaturation rate (RR for NAVA versus NCPAP: 0.69, 95%CI: 0.36 to 1.29; RR for NAVA versus NIPP: 0.58, 95%CI: 0.08 to 4.25), FiO2 (MD for NAVA versus NCPAP: –0.01, 95%CI: –0.04 to 0.02; MD for NAVA versus NIPP: –7.16, 95%CI: –22.63 to 8.31), and length of stay in the NICU (MD for NAVA versus NCPAP: 1.34, 95%CI: –4.17 to 6.85). Conclusion: NAVA showed similar clinical and ventilator-related outcomes compared to the usual care noninvasive respiratory support measures NCPAP or NIPP for preterm infants.

Keywords: preterm infants, noninvasive neurally adjusted ventilatory assist, NIV-NAVA, non-invasive ventilation, nasal continuous or positive airway pressure, NCPAP, intermittent positive airway pressure ventilation, NIPP, respiratory distress syndrome, RDS

Procedia PDF Downloads 80
230 SIPTOX: Spider Toxin Database Information Repository System of Protein Toxins from Spiders by Using MySQL Method

Authors: Iftikhar Tayubi, Tabrej Khan, Rayan Alsulmi, Abdulrahman Labban

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Spider produces a special kind of substance. This special kind of substance is called a toxin. The toxin is composed of many types of protein, which differs from species to species. Spider toxin consists of several proteins and non-proteins that include various categories of toxins like myotoxin, neurotoxin, cardiotoxin, dendrotoxin, haemorrhagins, and fibrinolytic enzyme. Protein Sequence information with references of toxins was derived from literature and public databases. From the previous findings, the Spider toxin would be the best choice to treat different types of tumors and cancer. There are many therapeutic regimes, which causes more side effects than treatment hence a different approach must be adopted for the treatment of cancer. The combinations of drugs are being encouraged, and dramatic outcomes are reported. Spider toxin is one of the natural cytotoxic compounds. Hence, it is being used to treat different types of tumors; especially its positive effect on breast cancer is being reported during the last few decades. The efficacy of this database is that it can provide a user-friendly interface for users to retrieve the information about Spiders, toxin and toxin protein of different Spiders species. SPIDTOXD provides a single source information about spider toxins, which will be useful for pharmacologists, neuroscientists, toxicologists, medicinal chemists. The well-ordered and accessible web interface allows users to explore the detail information of Spider and toxin proteins. It includes common name, scientific name, entry id, entry name, protein name and length of the protein sequence. The utility of this database is that it can provide a user-friendly interface for users to retrieve the information about Spider, toxin and toxin protein of different Spider species. The database interfaces will satisfy the demands of the scientific community by providing in-depth knowledge about Spider and its toxin. We have adopted the methodology by using A MySQL and PHP and for designing, we used the Smart Draw. The users can thus navigate from one section to another, depending on the field of interest of the user. This database contains a wealth of information on species, toxins, and clinical data, etc. This database will be useful for the scientific community, basic researchers and those interested in potential pharmaceutical Industry.

Keywords: siptoxd, php, mysql, toxin

Procedia PDF Downloads 151
229 Impact of Helicobacter pylori Infection on Colorectal Adenoma-Colorectal Carcinoma Sequence

Authors: Jannis Kountouras, Nikolaos Kapetanakis, Stergios A. Polyzos, Apostolis Papaeftymiou, Panagiotis Katsinelos, Ioannis Venizelos, Christina Nikolaidou, Christos Zavos, Iordanis Romiopoulos, Elena Tsiaousi, Evangelos Kazakos, Michael Doulberis

Abstract:

Background & Aims: Helicobacter pylori infection (Hp-I) has been recognized as a substantial risk agent involved in gastrointestinal (GI) tract oncogenesis by stimulating cancer stem cells (CSCs), oncogenes, immune surveillance processes, and triggering GI microbiota dysbiosis. We aimed to investigate the possible involvement of active Hp-I in the sequence: chronic inflammation–adenoma–colorectal cancer (CRC) development. Methods: Four pillars were investigated: (i) endoscopic and conventional histological examinations of patients with CRC, colorectal adenomas (CRA) versus controls to detect the presence of active Hp-I; (ii) immunohistochemical determination of the presence of Hp; expression of CD44, an indicator of CSCs and/or bone marrow-derived stem cells (BMDSCs); expressions of oncogene Ki67 and anti-apoptotic Bcl-2 protein; (iii) expression of CD45, indicator of immune surveillance locally (assessing mainly T and B lymphocytes locally); and (iv) correlation of the studied parameters with the presence or absence of Hp-I. Results: Among 50 patients with CRC, 25 with CRA, and 10 controls, a significantly higher presence of Hp-I in the CRA (68%) and CRC group (84%) were found compared with controls (30%). The presence of Hp-I with accompanying immunohistochemical expression of CD44 in biopsy specimens was revealed in a high proportion of patients with CRA associated with moderate/severe dysplasia (88%) and CRC patients with moderate/severe degree of malignancy (91%). Comparable results were also obtained for Ki67, Bcl-2, and CD45 immunohistochemical expressions. Concluding Remarks: Hp-I seems to be involved in the sequence: CRA – dysplasia – CRC, similarly to the upper GI tract oncogenesis, by several pathways such as the following: Beyond Hp-I associated insulin resistance, the major underlying mechanism responsible for the metabolic syndrome (MetS) that increase the risk of colorectal neoplasms, as implied by other Hp-I related MetS pathologies, such as non-alcoholic fatty liver disease and upper GI cancer, the disturbance of the normal GI microbiota (i.e., dysbiosis) and the formation of an irritative biofilm could contribute to a perpetual inflammatory upper GIT and colon mucosal damage, stimulating CSCs or recruiting BMDSCs and affecting oncogenes and immune surveillance processes. Further large-scale relative studies with a pathophysiological perspective are necessary to demonstrate in-depth this relationship.

Keywords: Helicobacter pylori, colorectal cancer, colorectal adenomas, gastrointestinal oncogenesis

Procedia PDF Downloads 118
228 Materials and Techniques of Anonymous Egyptian Polychrome Cartonnage Mummy Mask: A Multiple Analytical Study

Authors: Hanaa A. Al-Gaoudi, Hassan Ebeid

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The research investigates the materials and processes used in the manufacturing of an Egyptian polychrome cartonnage mummy mask with the aim of dating this object and establishing trade patterns of certain materials that were used and available at the time of ancient Egypt. This anonymous-source object was held in the basement storage of the Egyptian Museum in Cairo (EMC) and has never been on display. Furthermore, there is no information available regarding its owner, provenance, date, and even the time of its possession by the museum. Moreover, the object is in a very poor condition where almost two-thirds of the mask was bent and has never received any previous conservation treatment. This research has utilized well-established multi-analytical methods to identify the considerable diversity of materials that have been used in the manufacturing of this object. These methods include Computed Tomography Scan (CT scan) to acquire detailed pictures of the inside physical structure and condition of the bended layers. Dino-Lite portable digital microscope, scanning electron microscopy with energy dispersive X-ray spectrometer (SEM-EDX), and the non-invasive imaging technique of multispectral imaging (MSI) to obtain information about the physical characteristics and condition of the painted layers and to examine the microstructure of the materials. Portable XRF Spectrometer (PXRF) and X-Ray powder diffraction (XRD) to identify mineral phases and the bulk element composition in the gilded layer, ground, and pigments; Fourier-transform infrared (FTIR) to identify organic compounds and their molecular characterization; accelerator mass spectrometry (AMS 14C) to date the object. Preliminary results suggest that there are no human remains inside the object, and the textile support is linen fibres with tabby weave 1/1 and these fibres are in a very bad condition. Several pigments have been identified, such as Egyptian blue, Magnetite, Egyptian green frit, Hematite, Calcite, and Cinnabar; moreover, the gilded layers are pure gold and the binding media in the pigments is Arabic gum and animal glue in the textile support layer.

Keywords: analytical methods, Egyptian museum, mummy mask, pigments, textile

Procedia PDF Downloads 99
227 Development of a Mechanical Ventilator Using A Manual Artificial Respiration Unit

Authors: Isomar Lima da Silva, Alcilene Batalha Pontes, Aristeu Jonatas Leite de Oliveira, Roberto Maia Augusto

Abstract:

Context: Mechanical ventilators are medical devices that help provide oxygen and ventilation to patients with respiratory difficulties. This equipment consists of a manual breathing unit that can be operated by a doctor or nurse and a mechanical ventilator that controls the airflow and pressure in the patient's respiratory system. This type of ventilator is commonly used in emergencies and intensive care units where it is necessary to provide breathing support to critically ill or injured patients. Objective: In this context, this work aims to develop a reliable and low-cost mechanical ventilator to meet the demand of hospitals in treating people affected by Covid-19 and other severe respiratory diseases, offering a chance of treatment as an alternative to mechanical ventilators currently available in the market. Method: The project presents the development of a low-cost auxiliary ventilator with a controlled ventilatory system assisted by integrated hardware and firmware for respiratory cycle control in non-invasive mechanical ventilation treatments using a manual artificial respiration unit. The hardware includes pressure sensors capable of identifying positive expiratory pressure, peak inspiratory flow, and injected air volume. The embedded system controls the data sent by the sensors. It ensures efficient patient breathing through the operation of the sensors, microcontroller, and actuator, providing patient data information to the healthcare professional (system operator) through the graphical interface and enabling clinical parameter adjustments as needed. Results: The test data of the developed mechanical ventilator presented satisfactory results in terms of performance and reliability, showing that the equipment developed can be a viable alternative to commercial mechanical ventilators currently available, offering a low-cost solution to meet the increasing demand for respiratory support equipment.

Keywords: mechanical fans, breathing, medical equipment, COVID-19, intensive care units

Procedia PDF Downloads 41
226 Wood Diversity and Carbon Stock in Evergreen Forests in Cameroon: Case of the Ngambe-Ndom-Nyanon Communal Forest

Authors: Maffo Maffo Nicole Liliane, Mounmemi Kpoumie Hubert, Libalah Moses, Ouandji Angele, Zapfack Louis

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Forest degradation causes biodiversity and carbon loss and thus indirectly contributes to climate change. In order to assess the contribution of forests to climate change mitigation, the present study was conducted in the Ngambe-Ndom-Nyanon Communal Forest with the main objective of assessing the floristic diversity and estimating the carbon stock in the different reservoirs of the said forest. Nine plots of 2000 m² each were installed in 3 TOSs of the forest (young secondary forests, gallery forests and fallow lands) with a total area of 18,000 m² or 1,8 ha. All trees with a Diameter at Breast Height (DBH) ≥ 5 cm were inventoried at 1.30 m from the ground in each plot. Species richness, floristic diversity indices, and structural parameters were studied. 1542 trees divided into 162 species, 122 genera and 44 families were identified. The most important families were listed: Myristicaceae (30.22%), Apocynaceae (25.20%), Fabaceae (24.41%), Euphorbiaceae (22.91%) and Phyllanthaceae (20.23%). The richest genera are: Cola, Macaranga, Oncoba (4 species each); the genera Diospyros, Trichilia, Vitex and Zanthoxylum (3 species each). The ecologically important species within the forest studied are: Funtumia africana (26.14%), Coelocaryon preussii (18.46%), Pycnanthus angolensis (15.57%), Tabernaemontana crassa (14.85%) and Olax subscorpioidea (13.04%). Assessment of carbon stocks in the six forest reservoirs studied (living trees and roots, understorey, dead wood, litter and rootlets) shows that they vary according to the land-use types. It is 119.41 t.C.ha-¹ in gallery forest, 115.2 t.C.ha-¹ in young secondary forest and 90.56 t.C.ha-¹ in fallow. The Wilcoxon statistical test shows that the carbon in the young secondary forest is identical to that in the fallow, which is identical to the carbon in the gallery forest. At the individual species level, the largest diameter class [25-35[ sequesters the most carbon (232.94 tC/ha). This work shows that the quantity of carbon sequestered by a biotope is a function of the age of the stand.

Keywords: floristic diversity, carbon stocks, evergreen forests, communal forest, Ngambé-Ndom-Nyanon

Procedia PDF Downloads 27
225 Ficus Microcarpa Fruit Derived Iron Oxide Nanomaterials and Its Anti-bacterial, Antioxidant and Anticancer Efficacy

Authors: Fuad Abdullah Alatawi

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Microbial infections-based diseases are a significant public health issue around the world, mainly when antibiotic-resistant bacterium types evolve. In this research, we explored the anti-bacterial and anti-cancer potency of iron-oxide (Fe₂O₃) nanoparticles prepared from F. macrocarpa fruit extract. The chemical composition of F. macrocarpa fruit extract was used as a reducing and capping agent for nanoparticles’ synthesis was examined by GC-MS/MS analysis. Then, the prepared nanoparticles were confirmed by various biophysical techniques, including X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), UV-Vis Spectroscopy, and Transmission Electron Microscopy (TEM) and Energy Dispersive Spectroscopy (EDAX), and Dynamic Light Scattering (DLS). Also, the antioxidant capacity of fruit extract was determined through 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), Fluorescence Recovery After Photobleaching (FRAP), Superoxide Dismutase (SOD) assays. Furthermore, the cytotoxicity activities of Fe₂O₃ NPs were determined using the (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) (MTT) test on MCF-7 cells. In the antibacterial assay, lethal doses of the Fe₂O₃NPs effectively inhibited the growth of gram-negative and gram-positive bacteria. The surface damage, ROS production, and protein leakage are the antibacterial mechanisms of Fe₂O₃NPs. Concerning antioxidant activity, the fruit extracts of F. macrocarpa had strong antioxidant properties, which were confirmed by DPPH, ABTS, FRAP, and SOD assays. In addition, the F. microcarpa-derived iron oxide nanomaterials greatly reduced the cell viability of (MCF-7). The GC-MS/MS analysis revealed the presence of 25 main bioactive compounds in the F. microcarpa extract. Overall, the finding of this research revealed that F. microcarpa-derived Fe₂O₃ nanoparticles could be employed as an alternative therapeutic agent to cure microbial infection and breast cancer in humans.

Keywords: ficus microcarpa, iron oxide, antibacterial activity, cytotoxicity

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224 Computed Tomography Myocardial Perfusion on a Patient with Hypertrophic Cardiomyopathy

Authors: Jitendra Pratap, Daphne Prybyszcuk, Luke Elliott, Arnold Ng

Abstract:

Introduction: Coronary CT angiography is a non-invasive imaging technique for the assessment of coronary artery disease and has high sensitivity and negative predictive value. However, the correlation between the degree of CT coronary stenosis and the significance of hemodynamic obstruction is poor. The assessment of myocardial perfusion has mostly been undertaken by Nuclear Medicine (SPECT), but it is now possible to perform stress myocardial CT perfusion (CTP) scans quickly and effectively using CT scanners with high temporal resolution. Myocardial CTP is in many ways similar to neuro perfusion imaging technique, where radiopaque iodinated contrast is injected intravenously, transits the pulmonary and cardiac structures, and then perfuses through the coronary arteries into the myocardium. On the Siemens Force CT scanner, a myocardial perfusion scan is performed using a dynamic axial acquisition, where the scanner shuffles in and out every 1-3 seconds (heart rate dependent) to be able to cover the heart in the z plane. This is usually performed over 38 seconds. Report: A CT myocardial perfusion scan can be utilised to complement the findings of a CT Coronary Angiogram. Implementing a CT Myocardial Perfusion study as part of a routine CT Coronary Angiogram procedure provides a ‘One Stop Shop’ for diagnosis of coronary artery disease. This case study demonstrates that although the CT Coronary Angiogram was within normal limits, the perfusion scan provided additional, clinically significant information in regards to the haemodynamics within the myocardium of a patient with Hypertrophic Obstructive Cardio Myopathy (HOCM). This negated the need for further diagnostics studies such as cardiac ECHO or Nuclear Medicine Stress tests. Conclusion: CT coronary angiography with adenosine stress myocardial CTP was utilised in this case to specifically exclude coronary artery disease in conjunction with accessing perfusion within the hypertrophic myocardium. Adenosine stress myocardial CTP demonstrated the reduced myocardial blood flow within the hypertrophic myocardium, but the coronary arteries did not show any obstructive disease. A CT coronary angiogram scan protocol that incorporates myocardial perfusion can provide diagnostic information on the haemodynamic significance of any coronary artery stenosis and has the potential to be a “One Stop Shop” for cardiac imaging.

Keywords: CT, cardiac, myocardium, perfusion

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223 Biodegradation of Endoxifen in Wastewater: Isolation and Identification of Bacteria Degraders, Kinetics, and By-Products

Authors: Marina Arino Martin, John McEvoy, Eakalak Khan

Abstract:

Endoxifen is an active metabolite responsible for the effectiveness of tamoxifen, a chemotherapeutic drug widely used for endocrine responsive breast cancer and chemo-preventive long-term treatment. Tamoxifen and endoxifen are not completely metabolized in human body and are actively excreted. As a result, they are released to the water environment via wastewater treatment plants (WWTPs). The presence of tamoxifen in the environment produces negative effects on aquatic lives due to its antiestrogenic activity. Because endoxifen is 30-100 times more potent than tamoxifen itself and also presents antiestrogenic activity, its presence in the water environment could result in even more toxic effects on aquatic lives compared to tamoxifen. Data on actual concentrations of endoxifen in the environment is limited due to recent discovery of endoxifen pharmaceutical activity. However, endoxifen has been detected in hospital and municipal wastewater effluents. The detection of endoxifen in wastewater effluents questions the treatment efficiency of WWTPs. Studies reporting information about endoxifen removal in WWTPs are also scarce. There was a study that used chlorination to eliminate endoxifen in wastewater. However, an inefficient degradation of endoxifen by chlorination and the production of hazardous disinfection by-products were observed. Therefore, there is a need to remove endoxifen from wastewater prior to chlorination in order to reduce the potential release of endoxifen into the environment and its possible effects. The aim of this research is to isolate and identify bacteria strain(s) capable of degrading endoxifen into less hazardous compound(s). For this purpose, bacteria strains from WWTPs were exposed to endoxifen as a sole carbon and nitrogen source for 40 days. Bacteria presenting positive growth were isolated and tested for endoxifen biodegradation. Endoxifen concentration and by-product formation were monitored. The Monod kinetic model was used to determine endoxifen biodegradation rate. Preliminary results of the study suggest that isolated bacteria from WWTPs are able to growth in presence of endoxifen as a sole carbon and nitrogen source. Ongoing work includes identification of these bacteria strains and by-product(s) of endoxifen biodegradation.

Keywords: biodegradation, bacterial degraders, endoxifen, wastewater

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