Search results for: nonmelanoma skin cancer

Authors: Hui-Chi Huang, Su-Ju Yang, Ching-Wei Lin, Jui-Yao Tsai, Liang-Yiang

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Background: The most common serious complication following acute stroke is pneumonia. It has been associated with the increased morbidity, mortality, and medical cost after acute stroke in elderly patients. Purpose: The aim of this retrospective study was to investigate the relationship between stroke patients, risk factors of pneumonia, and one-year survival rates in a group of patients, in a tertiary referal center in Northern Taiwan. Methods: From January 2012 to December 2013, a total of 1730 consecutively administered stroke patients were recruited. The Survival analysis and multivariate regression analyses were used to examine the predictors for the one-year survival in stroke patients of a stroke registry database from northern Taiwan. Results: The risk of stroke mortality increased with age≧ 75 (OR=2.305, p < .0001), cancer (OR=3.221, p=<.0001), stayed in intensive care unit (ICU) (OR=2.28, p <.0006), dysphagia (OR=5.026, p<.0001), without speech therapy(OR=0.192, p < .0001),serum albumin < 2.5(OR=0.322, p=.0053) , eGFR > 60(OR=0.438, p <. 0001), admission NIHSS >11(OR=1.631, p=.0196), length of hospitalization (d) > 30(OR=0.608, p=.0227), and stroke subtype (OR=0.506, p=.0032). After adjustment of confounders, pneumonia was not significantly associated with the risk of mortality. However, it is most likely to develop in patients who are age ≧ 75, dyslipidemia , coronary artery disease , albumin < 2.5 , eGFR <60 , ventilator use , stay in ICU , dysphagia, without speech therapy , urinary tract infection , Atrial fibrillation , Admission NIHSS > 11, length of hospitalization > 30(d) , stroke severity (mRS=3-5) ,stroke Conclusion: In this study, different from previous research findings, we found that elderly age, severe neurological deficit and rehabilitation therapy were significantly associated with Post-stroke Pneumonia. However, specific preventive strategies are needed to target the high risk groups to improve their long-term outcomes after acute stroke. These findings could open new avenues in the management of stroke patients.

Keywords: stroke, risk, pneumonia, survival

Procedia PDF Downloads 216

Authors: Basant Singh Sikarwar, Mukesh Roy, Ayush Goyal, Priya Ranjan

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This work combines two bodies of knowledge which includes biomedical basis of blood stain formation and fluid communities’ wisdom that such formation of blood stain depends heavily on physical properties. Moreover biomedical research tells that different patterns in stains of blood are robust indicator of blood donor’s health or lack thereof. Based on these valuable insights an innovative screening tool is proposed which can act as an aide in the diagnosis of diseases such Anemia, Hyperlipidaemia, Tuberculosis, Blood cancer, Leukemia, Malaria etc., with enhanced confidence in the proposed analysis. To realize this powerful technique, simple, robust and low-cost micro-fluidic devices, a micro-capillary viscometer and a pendant drop tensiometer are designed and proposed to be fabricated to measure the viscosity, surface tension and wettability of various blood samples. Once prognosis and diagnosis data has been generated, automated linear and nonlinear classifiers have been applied into the automated reasoning and presentation of results. A support vector machine (SVM) classifies data on a linear fashion. Discriminant analysis and nonlinear embedding’s are coupled with nonlinear manifold detection in data and detected decisions are made accordingly. In this way, physical properties can be used, using linear and non-linear classification techniques, for screening of various diseases in humans and cattle. Experiments are carried out to validate the physical properties measurement devices. This framework can be further developed towards a real life portable disease screening cum diagnostics tool. Small-scale production of screening cum diagnostic devices is proposed to carry out independent test.

Keywords: blood, physical properties, diagnostic, nonlinear, classifier, device, surface tension, viscosity, wettability

Procedia PDF Downloads 356

Authors: Pedro Batista, André Vinha, Filipe Castelo, Bárbara Costa, Ricardo Sousa, Raquel Ricardo, André Pinto

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Background: Septic arthritis is a diagnosis that must be considered in any patient presenting with acute joint swelling and fever. Among the several risk factors for septic arthritis, such as age, rheumatoid arthritis, recent surgery, or skin infection, diabetes mellitus can sometimes be the main risk factor. Staphylococcus aureus is the most common pathogen isolated in septic arthritis; however, it is uncommon in monomicrobial necrotizing fasciitis. Objectives: A case report of concomitant septic arthritis and necrotizing fasciitis in a patient with undiagnosed diabetes based on clinical history. Study Design & Methods: We report a case of a 58-year-old Portuguese previously healthy man who presented to the emergency department with fever and left knee swelling and pain for two days. The blood work revealed ketonemia of 6.7 mmol/L and glycemia of 496 mg/dL. The vital signs were significant for a temperature of 38.5 ºC and 123 bpm of heart rate. The left knee had edema and inflammatory signs. Computed tomography of the left knee showed diffuse edema of the subcutaneous cellular tissue and soft tissue air bubbles. A diagnosis of septic arthritis and necrotising fasciitis was made. He was taken to the operating room for surgical debridement. The samples collected intraoperatively were sent for microbiological analysis, revealing infection by multi-sensitive Staphylococcus aureus. Given this result, the empiric flucloxacillin (500 mg IV) and clindamycin (1000 mg IV) were maintained for 3 weeks. On the seventh day of hospitalization, there was a significant improvement in subcutaneous and musculoskeletal tissues. After two weeks of hospitalization, there was no purulent content and partial closure of the wounds was possible. After 3 weeks, he was switched to oral antibiotics (flucloxacillin 500 mg). A week later, a urinary infection by Pseudomonas aeruginosa was diagnosed and ciprofloxacin 500 mg was administered for 7 days without complications. After 30 days of hospital admission, the patient was discharged home and recovered. Results: The final diagnosis of concomitant septic arthritis and necrotizing fasciitis was made based on the imaging findings, surgical exploration and microbiological tests results. Conclusions: Early antibiotic administration and surgical debridement are key in the management of septic arthritis and necrotizing fasciitis. Furthermore, risk factors control (euglycemic blood glucose levels) must always be taken into account given the crucial role in the patient's recovery.

Keywords: septic arthritis, Necrotizing fasciitis, diabetes, Staphylococcus Aureus

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Authors: Farhana Nosheen, Maleeha Fatima

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This study on Afghan refugee women living in Punjab, Pakistan, shows a strong relationship between poor socio-economic status and lower nutritional health status. Pakistan is one of the significant countries accepting refugees from the Afghan war. Universally, refugees are vulnerable to food security and basic life necessities. The in-hand study aimed to investigate food insecurity among afghan refugees who recently migrated to Pakistan. Purposive sampling technique was employed to collect the data from afghan women refugees settled in refugee camp settled in Capital city Islamabad, Pakistan. Data was collected through an interview tool. It revealed from data that the majority of women were underweight, about 74.7% in their reproductive years, which is an alarming situation for the forthcoming children and families. It is also shown that There’s a strong impact of their income level, education, dietary habits and food insecurity on their overall health status. It can also be observed in their Body Mass Index and in their physical appearance; they also show extremely poor levels of hemoglobin which is directly indicated anemic condition, especially iron deficiency anemia among the young Afghan refugee women. The illiteracy rate is about 93.33% among the selected participants as well as a majority of this population has 10-12 family size in comparison with their income level of about 10,000-15,000 Pakistani rupees per month, which can hardly meet their daily food expenditure. Adequate food is rarely accessible to young girls and women due to fewer national and international food aids program available in Pakistan. The majority have pale yellowish skin color (due to low iron content) along with clear white eyes (low hemoglobin level), thin hairs (protein deficiency) and spoon-shaped nails (a direct indicator of low iron level). Data showed a significant relation between appetite and BMI as their appetite is very low, which is directly indicated in their underweight body condition. About 56.67% of the participants had Urinary Tract Infections. The main causes included personal unhygienic conditions and lack of washrooms as well as drinking water facilities in their refugee camps. It is suggested that National and international food aid programs should cater to the nutritional demands of women refugees in the world to protect them from food insecurities as well as future researchers should find out better ways of analysis and treatment plans for such kind of communities who are highly prone to nutritional deficiencies and lack of basic supplies.

Keywords: food insecurity, refugees, women, vulnerable

Procedia PDF Downloads 79

Authors: Chengliang Xie, Jinhyun Ryu, Hyun Joon Kim, Gyeong Jae Cho, Wan Sung Choi, Sang Soo Kang, Kye Man Cho, Dong Hoon Lee

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Obesity has become a global health problem and a source of major metabolic diseases like type-2 diabetes, hypertension, heart disease, nonalcoholic fatty liver and cancer. Synthetic anti-obesity drugs are effective but very costly and with undesirable side effects, so natural products such as soybean are needed as an alternative for obesity treatment. Lactobacillus Plantarum P1201is a probiotic bacterial strain reported to produce conjugated linoleic acid (CLA) and increase the ratio of aglycone-isoflavone of soybean, both of which have anti-obesity effect. In this study, the anti-obesity effect of the fermented soybean extract with P1201 (FSE) will be evaluated compared with that of the soybean extract (SE) by 3T3-L1 cells as an in vitro model of adipogenesis. 3T3-L1 cells were treated with SE and FSE during the nine days of the differentiation, lipid accumulation was evaluated by oil-red staining and triglyceride content and the mRNA expression level of adipogenic or lipogenic genes were analyzed by RT-PCR and qPCR. The results showed that formation of lipid droplets in differentiated 3T3-L1 cells was inhibited and triglyceride content was reduced by 23.1% after treated with 1000 μg/mL of FSE compared with control. For SE-treated groups, no delipidating effect was observed. The effect of FSE on adipogenesis inhibition can be attributed to the down-regulation of mRNA expressionof CCAAT/enhancer binding protein (C/EBP-α), lipoprotein lipase (LPL), adiponectin, adipocyte fatty acid-binding protein (aP2), fatty acid synthesis (FAS) and CoA carboxylase (ACC). Our results demonstrated that the anti-obesity effect of soybean can be improved by fermentation with P1201, and P1201can be used as a potential probiotic bacterial strain to produce natural anti-obesity food.

Keywords: fermentation, Lactobacillus plantarum P1201, obesity, soybean

Procedia PDF Downloads 311

Authors: Panadda Rojpibulstit, Suthathip Kittisenachai, Songchan Puthong, Sirikul Manochantr, Pornpen Gamnarai, Sasichai Kangsadalampai, Sittiruk Roytrakul

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Hepatocellular carcinoma (HCC) is the most primary hepatic cancer worldwide. Nowadays a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is continually developed in HCC treatment. In this regard, after establishing and consequently exploring Hep88 mAb’s tumoricidal effect on hepatocellular carcinoma cell line (HepG2 cell line), the Hep88 mAb’s specific Ag from both membrane and cytoplasmic fractions of HepG2 cell line was identified by 2-D gel electrophoresis and western blot analysis. After in-gel digestion and subsequent analysis by liquid chromatography-mass spectrometry (LC-MS), mortalin (HSPA9) and alpha-enolase were identified. The recombinant proteins specific to Hep88 mAb were cloned and expressed in E.coli BL21 (DE3). Moreover, alteration of HepG2 and Chang liver cell line after being induced by Hep88 mAb for 1-3 days was investigated using a transmission electron microscope. The result demonstrated that Hep88 mAb can bind to the recombinant mortalin (HSPA9) andalpha-enolase. In addition, gradual appearance of mitochondria vacuolization and endoplasmic reticulum dilatation were observed. Taken together, paraptosis-like programmed cell death (PCD) of HepG2 is induced by binding of mortalin (HSPA9) and alpha-enolase to Hep88 mAb. Mortalin depletion by formation of Hep88 mAb-mortalin (HSPA9) complex might initiate transcription-independent of p53-mediated apoptosis. Additionally, Hep88 mAb-alpha-enolase complex might initiate HepG2 cells energy exhaustion by glycolysis pathway obstruction. These results imply that Hep88 mAb might be a promising tool for development of an effective treatment of HCC in the next decade.

Keywords: Hepatocellular carcinoma, Monoclonal antibody, Paraptosis-like program cell death, Transmission electron microscopy, mortalin (HSPA9), alpha-enolase

Procedia PDF Downloads 339

Authors: Pedro Cabrales, Scott Caroen, Tony R. Reid, Bryan Oronsky

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Introduction and Purpose RRx-001 is an NLRP3 inhibitor and Nrf2 agonist in Phase 3 trials for the treatment of cancer. The purpose of this study was to examine whether treatment with RRx-001, given itsanti-inflammatory and antioxidant properties, improvedexercise and skeletal muscle oxidative capacity in mice on the generalpremiss that better health outcomes correlatewith more activity. Material and Methods Male and female adult mice (n=6 per group) were subjected to an endurance exercise capacity (EEC)test until exhaustion on a motorized treadmill after 3 once weekly doses of either RRx-001 5 mg/kg, RRx-001 2 mg/kg, or vehicle. The EEC protocol consisted of a treadmill velocity of 30meters per min at an uphill inclination (slope of 10%) until the mice reached fatigue, which was defined as the inability of the mice to maintain the appropriate pace despitecontinuous hand stimulation for 1 min. The concentration of malondialdehyde (MDA), an indicator of lipid peroxidation, and creatine kinase (CK), an indicator of muscle damage, in the blood samples collected immediately after the acute exercise was determined with a commercial ELISA assay kit. ResultsThe exhaustive exercise times of the RRx-001 groups were significantly longer than that of the vehicle group (p<0.05) by weeks 2 and 3. In addition, MDA levels in the gastrocnemius, soleus, and extensor digitorum longus muscles were significantly lower than those of the vehicle group were (p<0.05), as were the serum CK levels(p<0.05). ConclusionsIn conclusion, this study found that RRx-001 has anti-fatigue properties, as evidenced by an increase in exercise capacity with RRx-001 treatment, and protects against strenuous exercise-induced muscle damage and lipid peroxidation. This data potentially supports the use of RRx-001 in the clinic to improve exercise performance and reduce physical fatigue.

Keywords: RRx-001, anti-fatigue, muscle protection, increased exercise tolerance, lipid peroxidation

Procedia PDF Downloads 79

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

Procedia PDF Downloads 62

Authors: Nejla Fourati, Zied Fessi, Fatma Dhouib, Wicem Siala, Leila Farhat, Afef Khanfir, Wafa Mnejja, Jamel Daoud

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Purpose: Radiation induced hypothyroidism in nasopharyngeal cancer (NPC) ranged from 15% to 55%. In reported data, it is considered as a common late complication of definitive radiation and is mainly observed 2 years after the end of treatment. The aim of this study was to evaluate the incidence of early hypothyroidism within 6 months after radiotherapy. Patients and methods: From June 2017 to February 2020, 35 patients treated with concurrent chemo-radiotherapy (CCR) for NPC were included in this prospective study. Median age was 49 years [23-68] with a sex ratio of 2.88. All patients received intensity modulated radiotherapy (IMRT) at a dose of 69.96 Gy in 33 daily fractions with weekly cisplatin (40mg/m²) chemotherapy. Thyroid stimulating hormone (TSH) and Free Thyroxine 4 (FT4) dosage was performed before the start of radiotherapy and 6 months after. Different dosimetric parameters for the thyroid gland were reported: the volume (cc); the mean dose (Dmean) and the %age of volume receiving more than 45 Gy (V45Gy). Wilcoxon Test was used to compare these different parameters between patients with or without hypothyroidism. Results: At baseline, 5 patients (14.3%) had hypothyroidism and were excluded from the analysis. For the remaining 30 patients, 9 patients (30%) developed a hypothyroidism 6 months after the end of radiotherapy. The median thyroid volume was 10.3 cc [4.6-23]. The median Dmean and V45Gy were 48.3 Gy [43.15-55.4] and 74.8 [38.2-97.9] respectively. No significant difference was noted for all studied parameters. Conclusion: Early hypothyroidism occurring within 6 months after CCR for NPC seems to be a common complication (30%) that should be screened. Good patient monitoring with regular dosage of TSH and FT4 makes it possible to treat hypothyroidism in asymptomatic phase. This would be correlated with an improvement in the quality of life of these patients. The results of our study do not show a correlation between the thyroid doses and the occurrence of hypothyroidism. This is probably related to the high doses received by the thyroid in our series. These findings encourage more optimization to limit thyroid doses and then the risk of radiation-induced hypothyroidism

Keywords: nasopharyngeal carcinoma, hypothyroidism, early complication, thyroid dose

Procedia PDF Downloads 108

Authors: Anne Heirman, Vincent van der Noort, Rob van Son, Marije Petersen, Lisette van der Molen, Gyorgy Halmos, Richard Dirven, Michiel van den Brekel

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Objective: Voice prosthesis leakage significantly impacts laryngectomies patients' quality of life, causing insecurity and frequent unplanned hospital visits and costs. In this study, the concept of prophylactic voice prosthesis replacement was explored to prevent leakages. Study Design: A retrospective cohort study. Setting: Tertiary hospital. Methods: Device lifetimes and voice prosthesis replacements of a retrospective cohort, including all patients with laryngectomies between 2000 and 2012 in the Netherlands Cancer Institute, were used to calculate the number of needed voice prostheses per patient per year when preventing 70% of the leakages by prophylactic replacement. Various strategies for the timing of prophylactic replacement were considered: Adaptive strategies based on the individual patient’s history of replacement and fixed strategies based on the results of patients with similar voice prosthesis or treatment characteristics. Results: Patients used a median of 3.4 voice prostheses per year (range 0.1-48.1). We found a high inter-and intrapatient variability in device lifetime. When applying prophylactic replacement, this would become a median of 9.4 voice prostheses per year, which means replacement every 38 days, implying more than six additional voice prostheses per patient per year. The individual adaptive model showed that preventing 70% of the leakages was impossible for most patients, and only a median of 25% can be prevented. Monte-Carlo simulations showed that prophylactic replacement is not feasible due to the high Coefficient of Variation (Standard Deviation/Mean) in device lifetime. Conclusion: Based on our simulations, prophylactic replacement of voice prostheses is not feasible due to high inter-and intrapatient variation in device lifetime.

Keywords: voice prosthesis, voice rehabilitation, total laryngectomy, prosthetic leakage, device lifetime

Procedia PDF Downloads 106

Authors: Malik Muhammad Arslan, Muneeb Ullah, Dai Shihan, Daniyal Haider, Xiaodong Yang

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Chest X-rays are instrumental in the detection and monitoring of a wide array of diseases, including viral infections such as COVID-19, tuberculosis, pneumonia, lung cancer, and various cardiac and pulmonary conditions. To enhance the accuracy of diagnosis, artificial intelligence (AI) algorithms, particularly deep learning models like Convolutional Neural Networks (CNNs), are employed. However, these deep learning models demand a substantial and varied dataset to attain optimal precision. Generative Adversarial Networks (GANs) can be employed to create new data, thereby supplementing the existing dataset and enhancing the accuracy of deep learning models. Nevertheless, GANs have their limitations, such as issues related to stability, convergence, and the ability to distinguish between authentic and fabricated data. In order to overcome these challenges and advance the detection and classification of CXR normal and abnormal images, this study introduces a distinctive technique known as DCWGAN (Diverse Conditional Wasserstein GAN) for generating synthetic chest X-ray (CXR) images. The study evaluates the effectiveness of this Idiosyncratic DCWGAN technique using the ResNet50 model and compares its results with those obtained using the traditional GAN approach. The findings reveal that the ResNet50 model trained on the DCWGAN-generated dataset outperformed the model trained on the classic GAN-generated dataset. Specifically, the ResNet50 model utilizing DCWGAN synthetic images achieved impressive performance metrics with an accuracy of 0.961, precision of 0.955, recall of 0.970, and F1-Measure of 0.963. These results indicate the promising potential for the early detection of diseases in CXR images using this Inimitable approach.

Keywords: CNN, classification, deep learning, GAN, Resnet50

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Authors: Amalia Ardeljan, Lexi Frankel, Divesh Manjani, Gabriela Santizo, Maximillian Guerra, Omar Rashid

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Introduction: Cytomegalovirus (CMV) infection is a widespread infection affecting between 60-70% of people in industrialized countries. CMV has been previously correlated with a higher incidence of Hodgkin Lymphoma compared to noninfected persons. Research regarding prior CMV infection and subsequent lymphoma development is still controversial. With limited evidence, further research is needed in order to understand the relationship between previous CMV infection and subsequent lymphoma development. This study assessed the effect of CMV infection and the incidence of lymphoma afterward. Methods: A retrospective cohort study (2010-2019) was conducted through a Health Insurance Portability and Accountability Act (HIPAA) compliant national database and conducted using International Classification of Disease (ICD) 9th,10th codes, and Current Procedural Terminology (CPT) codes. These were used to identify lymphoma diagnosis in a previously CMV infected population. Patients were matched for age range and Charlson Comorbidity Index (CCI). A chi-squared test was used to assess statistical significance. Results: A total number of 14,303 patients was obtained in the CMV infected group as well as in the control population (matched by age range and CCI score). Subsequent lymphoma development was seen at a rate of 11.44% (1,637) in the CMV group and 5.74% (822) in the control group, respectively. The difference was statistically significant by p= 2.2x10-16, odds ratio = 2.696 (95% CI 2.483- 2.927). In an attempt to stratify the population by antiviral medication exposure, the outcomes were limited by the decreased number of members exposed to antiviral medication in the control population. Conclusion: This study shows a statistically significant correlation between prior CMV infection and an increased incidence of lymphoma afterward. Further exploration is needed to identify the potential carcinogenic mechanism of CMV and whether the results are attributed to a confounding bias.

Keywords: cytomegalovirus, lymphoma, cancer, microbiology

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Authors: Maatouk Mohamed, Nouira Mariem, Hamdi Kbir Gh, Mahjoubi M. F., Ben Moussa M.

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Background and aim: Preoperative biliary drainage (PBD) has been introduced to lower bilirubin levels and to control the negative effects of obstructive jaundice in patients with malignant obstructive jaundice undergoing pancreaticoduodenectomy (PD). The optimal time interval between PBD and PD is still not clear. Delaying surgery by 4 to 6 weeks is the commonly accepted practice. However, delayed PD has been shown to decrease the rate of resection and adversely affect the tumor grading and prognosis. Thus, the purpose of our systematic review and meta-analysis was to evaluate the optimal period for PBD prior to PD: short or prolonged in terms of postoperative morbidity and survival outcomes. Methods: Trials were searched in PubMed, Science Direct, Google Scholar, and Cochrane Library until November 2022. Studies using PBD in patients with malignant obstructive jaundice that compared short duration group (SDG) (surgery performed within 3-4 weeks) with prolonged duration group (PDG) (at least 3-4 weeks after PBD) were included in this study. The risk of bias was assessed using the Rob v2 and Robins-I tools. The priori protocol was published in PROSPERO (ID: CRD42022381405). Results: Seven studies comprising 1625 patients (SDG 870, PDG 882) were included. All studies were non-randomized, and only one was prospective. No significant differences were observed between the SDG and PDG in mortality (OR= 0.59; 95% CI [0.30, 1.17], p=0.13), major morbidity (Chi² = 30.28, p <0.00001; I² = 87%), pancreatic fistula (Chi² = 6.61, p = 0.25); I² = 24%), post pancreatectomy haemorrhage (OR= 1.16; 95% CI [0.67, 2.01], p=0.59), positive drainage culture (OR= 0.36; 95% CI [0.10, 1.32], p=0.12), septic complications (OR= 0.78; 95% CI [0.23, 2.72], p=0.70), wound infection (OR= 0.08, p=0.07), operative time (MD= 0.21; p=0.21). Conclusion: Early surgery within 3 or 4 weeks after biliary drainage is both safe and effective. Thus, it is reasonable to suggest early surgery following PBD for patients having resectable periampullary cancers.

Keywords: preoperative biliary drainage, pancreatic cancer, pancreatic surgery, complication

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Authors: Chodidjah, Edi Dharmana, Hardhono, Sarjadi

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Breast cancer treatment options including surgery, radiation therapy, chemotherapy, and immunotherapy have not been effective. Besides, they have side effects. Keladi Tikus (Typhonium flagelliforme) has been shown to improve immune system, suppress tumor growth and induce apoptosis. One of the parameters for immune system, tumor growth and apoptosis is IFNγ (Interferon γ), VEGF (Vascular Endothelial Growth Factor) and Caspase 3 respectively. The aim of this study was to examine the effect of the administration of Keladi Tikus tuber extract at the dose of 200 mg/kgBW, 400 mg/KgBW, and 800 mg/kgBW on the level of IFNγ, VEGF and caspase 3 expression. In this experimental study using post test randomized control group design, 24 CH3 mice with tumor were randomly divided into 4 groups including control group and treated groups: Treated with 0.2 cc extract of Keladi Tikus at the dose of 200 mg/kgBW, 400 mg/kgBW, 800 mg/kgBW, respectively for 30 days. On day 31 the lymphatic tissue was taken and evaluated for its level of IFNγ, using ELISA. The tumor tissue was taken and subjected to immunohistochemistry staining for VEGF and caspase 3 expression evaluation. The data on IFNγ, VEGF and Caspase 3 expression were analyzed using One Way Anova with significant level of 0.05. One Way Anova resulted in p<0.05. LSD test showed that the level of IFNγ and Caspase 3 for control group was different from that of treated groups. There was no significant different between the treated group of 400 mg/KgBW and 800mg/KgBW. VEGF expressions for all the treated groups were significant. In conclusion, the oral administration of ethanolic extract of Keladi Tikus (Typhonium flagelliforme) at the dose of 200mg/kgBW, 400 mg/kgBW,800 mg/kgBW increases IFNγ, Caspase 3 and decreases VEGF expression in C3H mice with adenocarsinoma mamma.

Keywords: Typhonium flagelliforme, IFNγ, caspase 3, VEGF

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Authors: Mualla McManus, Jenna Luche Thaye

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World Health Organisation International Classification of Disease codes were created to define disease including infections in order to guide and educate diagnosticians. Most infectious diseases such as syphilis are clearly defined by their ICD 10 codes and aid/help to educate the clinicians in syphilis diagnosis and treatment globally. However, current ICD 10 codes for relapsing fever Borreliosis and Lyme disease are less clearly defined and can impede appropriate diagnosis especially if the clinician is not familiar with the symptoms of these infectious diseases. This is despite substantial number of scientific articles published in peer-reviewed journals about relapsing fever and Lyme disease. In the USA there are estimated 380,000 people annually contacting Lyme disease, more cases than breast cancer and 6x HIV/AIDS cases. This represents estimated 0.09% of the USA population. If extrapolated to the global population (7billion), 0.09% equates to 63 million people contracting relapsing fever or Lyme disease. In many regions, the rate of contracting some form of infection from tick bite may be even higher. Without accurate and appropriate diagnostic codes, physicians are impeded in their ability to properly care for their patients, leaving those patients invisible and marginalized within the medical system and to those guiding public policy. This results in great personal hardship, pain, disability, and expense. This unnecessarily burdens health care systems, governments, families, and society as a whole. With accurate diagnostic codes in place, robust data can guide medical and public health research, health policy, track mortality and save health care dollars. Better defined ICD codes are the way forward in educating the diagnosticians about relapsing fever and Lyme diseases.

Keywords: WHO ICD codes, relapsing fever, Lyme diseases, World Health Organisation

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Authors: Nurunnahar Akter, Elena Kulinskaya, Nicholas Steel, Ilyas Bakbergenuly

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Although Hormone Replacement Therapy (HRT) is an effective treatment in ameliorating menopausal symptoms, it has mixed effects on different health outcomes, increasing, for instance, the risk of breast cancer. Because of this, many symptomatic women are left untreated. Untreated menopausal symptoms may result in other health issues, which eventually put an extra burden and costs to the health care system. All-cause mortality analysis may explain the net benefits and risks of the HRT therapy. However, it received far less attention in HRT studies. This study investigated the impact of HRT on all-cause mortality using electronically recorded primary care data from The Health Improvement Network (THIN) that broadly represents the female population in the United Kingdom (UK). The study entry date for this study was the record of the first HRT prescription from 1984, and patients were followed up until death or transfer to another GP practice or study end date, which was January 2017. 112,354 HRT users (cases) were matched with 245,320 non-users by age at HRT initiation and general practice (GP). The hazards of all-cause mortality associated with HRT were estimated by a parametric Weibull-Cox model adjusting for a wide range of important medical, lifestyle, and socio-demographic factors. The multilevel multiple imputation techniques were used to deal with missing data. This study found that during 32 years of follow-up, combined HRT reduced the hazard ratio (HR) of all-cause mortality by 9% (HR: 0.91; 95% Confidence Interval, 0.88-0.94) in women of age between 46 to 65 at first treatment compared to the non-users of the same age. Age-specific mortality analyses found that combined HRT decreased mortality by 13% (HR: 0.87; 95% CI, 0.82-0.92), 12% (HR: 0.88; 95% CI, 0.82-0.93), and 8% (HR: 0.92; 95% CI, 0.85-0.98), in 51 to 55, 56 to 60, and 61 to 65 age group at first treatment, respectively. There was no association between estrogen-only HRT and women’s all-cause mortality. The findings from this study may help to inform the choices of women at menopause and to further educate the clinicians and resource planners.

Keywords: hormone replacement therapy, multiple imputations, primary care data, the health improvement network (THIN)

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Authors: Jemini Vyas, Oluwatobi Adeyoe, Jenny Branagan, Chandran Tanabalan, John Beatty, Aakash Pai

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Introduction: The development of robotic surgery has accelerated centralisation to tertiary centres, where robotic radical prostatectomy (RP) is offered. The purpose of concentrating treatment in high volume specialist centres is to improve the quality of care and patient outcomes. The aim of this study was to assess the impact on clinical outcomes of centralisation for locally diagnosed patients undergoing RP. Methods: Clinical outcomes for 169 consecutive laparoscopic & open RP pre-centralisation were retrospectively compared with 50 consecutive robotic RP conducted over a similar period post-centralisation. Preoperative risk stratification and time to surgery were collected. Perioperative outcomes, including length of stay (LOS) and complications, were collated. Post-operative outcomes, including erectile dysfunction (ED), biochemical recurrence (BCR), and urinary continence, were assessed. Results: Preoperative risk stratification showed no difference between the two groups. The median time from diagnosis to treatment was similar between the two groups (pre-centralisation, 121 days, post-centralisation, 117 days). The mean length of stay (pre-centralisation, 2.1 days, post-centralisation, 1.6 days) showed no significant difference (p=0.073). Proportion of overall complications (pre-centralisation, 11.4%, post-centralisation, 8.7%) and complications, above Clavien-Dindo 2, were similar between the two groups (pre-centralisation1.2%, post-centralisation 2.2%). Post operative functional parameters, including continence and ED, were comparable. Five-year BCR free rate was 78% for the pre-centralisation group and 79% for the post centralisation group. Conclusion: For our cohort of patients, clinical outcomes have remained static during centralisation. It is imperative that centralisation is accompanied by increased capacity, streamlining of pathways, and training to ensure that improved quality of care is achieved. Our institution has newly acquired a robot, and prospectively studying this data may support the reversal of centralisation for RP surgery.

Keywords: prostate, cancer, prostatectomy, clinical

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Authors: Gilda Santos, Rita Marques, Francisca Marques, João Ribeiro, André Fonseca, João M. Miranda, João B. L. M. Campos, Soraia F. Neves

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Every year, an unacceptable number of firefighters are seriously burned during firefighting operations, with some of them eventually losing their life. Although thermal protective clothing research and development has been searching solutions to minimize firefighters heat load and skin burns, currently commercially available solutions focus in solving isolated problems, for example, radiant heat or water-vapor resistance. Therefore, episodes of severe burns and heat strokes are still frequent. Taking this into account, a consortium composed by Portuguese entities has joined synergies to develop an innovative protective clothing system by following a procedure based on the application of numerical models to optimize the design and using a combinationof protective clothing components disposed in different layers. Recently, it has been shown that Phase Change Materials (PCMs) can contribute to the reduction of potential heat hazards in fire extinguish operations, and consequently, their incorporation into firefighting protective clothing has advantages. The greatest challenge is to integrate these materials without compromising garments ergonomics and, at the same time, accomplishing the International Standard of protective clothing for firefighters – laboratory test methods and performance requirements for wildland firefighting clothing. The incorporation of PCMs into the firefighter's protective jacket will result in the absorption of heat from the fire and consequently increase the time that the firefighter can be exposed to it. According to the project studies and developments, to favor a higher use of the PCM storage capacityand to take advantage of its high thermal inertia more efficiently, the PCM layer should be closer to the external heat source. Therefore, in this stage, to integrate PCMs in firefighting clothing, a mock-up of a vest specially designed to protect the torso (back, chest and abdomen) and to be worn over a fire-resistant jacketwas envisaged. Different configurations of PCMs, as well as multilayer approaches, were studied using suitable joining technologies such as bonding, ultrasound, and radiofrequency. Concerning firefighter’s protective clothing, it is important to balance heat protection and flame resistance with comfort parameters, namely, thermaland water-vapor resistances. The impact of the most promising solutions regarding thermal comfort was evaluated to refine the performance of the global solutions. Results obtained with experimental bench scale model and numerical simulation regarding the integration of PCMs in a vest designed as protective clothing for firefighters will be presented.

Keywords: firefighters, multilayer system, phase change material, thermal protective clothing

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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Non-alcoholic steatohepatitis (NASH) is a chronic liver disease, often associated with type II diabetes, which sometimes progresses to more serious conditions such as liver fibrosis and hepatocellular carcinoma (HCC). NASH has become an important health problem worldwide, buttherapeutic agents for NASH have not yet been approved, and animal models with high clinical correlation are required. TheSTAM™ mouse shows the same pathological progression as human NASH patients and has been widely used for both drug efficacy and basic research, such as lipid profiling and gut microbiota research. In this study, we analyzed the RNA-seq data of STAM™mice at each pathological stage (steatosis, steatohepatitis, liver fibrosis, and HCC) and examined the clinical correlation at the genetic level. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin solution 2 days after birth and feeding with high fat dietafter 4 weeks of age. The mice were sacrificed and livers collected at 6, 8, 10, 12, 16, and 20 weeks of age. For liver samples, the left lateral lobe was snap frozen in liquid nitrogen and stored at -80˚C for RNA-seq analysis. Total RNA of the cells was isolated using RNeasy mini kit. The gene expression of the canonical pathways in NASH progression from steatosis to hepatocellular carcinoma were analyzed, such as immune system process, oxidation-reduction process, lipid metabolic process. Moreover, since it has been reported that genetic traits are involved in the development of NASH-HCC, we next analyzed the genetic mutations in the STAM™mice. The number of individuals showing mutations in Mtorinvolved in Insulin signaling increases as the disease progresses, especially in the liver cancer phase. These results indicated a clinical correlation of gene profiles in the STAM™mouse.

Keywords: steatosis, non-alcoholic steatohepatitis, fibrosis, hepatocellular carcinoma, RNA-seq

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Authors: Valeriu Mihai But, Sorana Daniela Bolboacă, Adriana Elena Bulboacă

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The nutraceutical compound Curcumin (Curcuma longa L.) is known for its anti-inflammatory, anti-cancer, and antioxidant effects. This study aimed to evaluate the antioxidative and analgesic effects of Curcumin (CC) compared to Tramadol (T) in chemical-induced nociceptive pain in rats. Thirty-five rats were randomly divided into five groups of seven rats each and were treated as follows: C group (control group): treated with saline solution 0.9%, (1 ml, i.p. administration), ethanoic acid (EA) group: pretreated with saline solution 0.9% - 30 min before EA nociceptive pain induction, (1 ml, i.p. administration), T group: pretreated with Tramadol, 10 mg/kg body weight (bw), i.p. administration - 30 min before EA nociceptive pain induction, CC1-group: pretreated with 1 mg/100g bw Curcumin i.p. administration - 2 days before EA pain induction and CC2-group: pretreated with Curcumin 2 mg/100g bw i.p. administration - 2 days before EA nociceptive pain induction. The following oxidative stress parameters were assessed: malondialdehyde (MDA), nitric oxide (NOx), total oxidative status (TOS), total antioxidative capacity (TAC), and thiol (Th). The antalgic activity was measured by the ethanoic acid writhing test. Treatment with Curcumin, both 1 mg/100g bw, and 2 mg/100g bw, showed significant differences as compared with the control group (p<0.001) regarding malondialdehyde (MDA), nitric oxide (NOx), and total oxidative status (TOS) oxidative biomarkers. Pretreatment with 2 mg/100g bw of Curcumin presented a significant decrease in MDA values compared with Tramadol (p<0.001). The TAC significantly increased in pretreatment with Curcumin compared with group control. (p<0.001) The nociceptive response to EA was significantly reduced in Curcumin and Tramadol groups. Treatment with Curcumin at a higher concentration was more effective. In an experimental pain model, this study demonstrates an important antioxidant and antinociceptive activity of Curcumin comparable with Tramadol treatment.

Keywords: curcumin, nociception, oxidative stress, pain

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Authors: Shabnam Sarwar, Franck Lacoeuille, Nadia Withofs, Roland Hustinx

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After the development of a potential surrogate of MAA, and its successful application for the diagnosis of pulmonary embolism in artificially embolized rats’ lungs, this microparticulate system were radiolabelled with gallium-68 to synthesize 68Ga-SBMP with high radiochemical purity >99%. As a prerequisite step of clinical trials, 68Ga- labelled starch based microparticles (SBMP) were analysed for their in-vivo behavior in small animals. The purpose of the presented work includes the ex-vivo biodistribution studies of 68Ga-SBMP in order to assess the activity uptake in target organs with respect to time, excretion pathways of the radiopharmaceutical, %ID/g in major organs, T/NT ratios, in-vivo stability of the radiotracer and subsequently the microparticles in the target organs. Radiolabelling of starch based microparticles was performed by incubating it with 68Ga generator eluate (430±26 MBq) at room temperature and pressure without using any harsh reaction condition. For Ex-vivo biodistribution studies healthy White Wistar rats weighing between 345-460 g were injected intravenously 68Ga-SBMP 20±8 MBq, containing about 2,00,000-6,00,000 SBMP particles in a volume of 700µL. The rats were euthanized at predefined time intervals (5min, 30min, 60min and 120min) and their organ parts were cut, washed, and put in the pre-weighed tubes and measured for radioactivity counts through automatic Gamma counter. The 68Ga-SBMP produced >99% RCP just after 10-20 min incubation through a simple and robust procedure. Biodistribution of 68Ga-SBMP showed that initially just after 5 min post injection major uptake was observed in the lungs following by blood, heart, liver, kidneys, bladder, urine, spleen, stomach, small intestine, colon, skin and skeleton, thymus and at last the smallest activity was found in brain. Radioactivity counts stayed stable in lungs with gradual decrease with the passage of time, and after 2h post injection, almost half of the activity were seen in lungs. This is a sufficient time to perform PET/CT lungs scanning in humans while activity in the liver, spleen, gut and urinary system decreased with time. The results showed that urinary system is the excretion pathways instead of hepatobiliary excretion. There was a high value of T/NT ratios which suggest fine tune images for PET/CT lung perfusion studies henceforth further pre-clinical studies and then clinical trials should be planned in order to utilize this potential lung perfusion agent.

Keywords: starch based microparticles, gallium-68, biodistribution, target organs, excretion pathways

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Authors: Alakija Temitope Olufunmilayo, Akinyemi, Yagba Joy

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Hepatitis is the inflammation of the liver tissue that can cause whiteness of the eyes (Jaundice), lack of appetite, vomiting, tiredness, abdominal pain, diarrhea. Hepatitis is acute if it resolves within 6 months and chronic if it last longer than 6 months. Acute hepatitis can resolve on its own, lead to chronic hepatitis or rarely result in acute liver failure. Chronic hepatitis may lead to scarring of the liver (Cirrhosis), liver failure and liver cancer. Modelling Hepatitis B may become necessary in order to reduce its spread. So, dynamic SIR model can be used. This model consists of a system of three coupled non-linear ordinary differential equation which does not have an explicit formula solution. It is an epidemiological model used to predict the dynamics of infectious disease by categorizing the population into three possible compartments. In this study, a five-compartment dynamic model of Hepatitis B disease was proposed and developed by adding control measure of sensitizing the public called awareness. All the mathematical and statistical formulation of the model, especially the general equilibrium of the model, was derived, including the nonlinear least square estimators. The initial parameters of the model were derived using nonlinear least square embedded in R code. The result study shows that the proportion of Hepatitis B patient in the study population is 1.4 per 1,000,000 populations. The estimated Hepatitis B induced death rate is 0.0108, meaning that 1.08% of the infected individuals die of the disease. The reproduction number of Hepatitis B diseases in Nigeria is 6.0, meaning that one individual can infect more than 6.0 people. The effect of sensitizing the public on the basic reproduction number is significant as the reproduction number is reduced. The study therefore recommends that programme should be designed by government and non-governmental organization to sensitize the entire Nigeria population in order to reduce cases of Hepatitis B disease among the citizens.

Keywords: hepatitis B, modelling, non-linear ordinary differential equation, sihar model, sensitization

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Authors: Nantale Prossy Nabatte, Josephat Nyagero, Elizabeth Kemigisha

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Background: Human Papilloma Virus (HPV) is a prevalent sexually transmitted infection (STI) in the world. It is important to screen for HPV so that women found positive receive early treatment to prevent the development of cervical cancer. The broad aim of the research was to explore the types, occurrence, and associated correlates of HPV infection by genotyping Human papillomavirus among a cohort of WLHIV attending an antiretroviral therapy clinic in Mukono, Uganda. Methods: A cross-sectional study was used to collect data for socio-demographic, sexual practices, and medical history factors associated with HPV genotypes using a pretested interview guide subjected to 342 WLHIV. The respondents’ results for HPV genotypes were obtained retrospectively from respective laboratory records. Data was entered in Epidata v4.6 and analysed using STATA V14. The prevalence of hr-HPV was estimated as a proportion of the entire sample size. Analysis for the correlates of hr-HPV infection was done using a modified Poisson regression model. Results: Slightly more than a half of respondents were aged below 35 years (56.7%), married (52.6%), and with a primary level of education (51.2%). The prevalence of hr-HPV was 39.8% at a 95% confidence interval (CI: 34.40- 44.78). The hr-HPV was higher among those between 30-34 years of age (n= 41, 30.2%) than those between the age of 45-49 years (n=16, 11.8%). In terms of associated correlates, age 45-49 years (aPR: 1.95, 95% CI: 1.41- 2.69), being married (aPR: 1.30, 95% CI: 1.00, 1.69), use of condoms (aPR: 1.31, 95% CI: 1.00 -1.71) and age of sexual debut (aPR: 1.42, 95% CI: 1.08-1.87) were significantly associated with Human papillomavirus genotypes. Conclusion and Recommendation: The prevalence of hr-HPV infection was high, indicative of a risk to the health of WLHIV in Mukono, Uganda, and worldwide at large. The correlates are age 45-49 years, being married, use of condoms, and age of sexual debut. Based on the results, it is recommended that the implementing teams in such projects put more emphasis on the diagnosis of hr-HPV infection and monitoring the treatment. More research is required to determine the effect of ART therapy on hr-HPV persistence.

Keywords: human papillomavirus genotypes, and their correlates, among women living with HIV, attending antiretroviral clinic

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Authors: Parimelazhagan Thangaraj

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Natural products serves human kind as a source of all drugs and higher plants provide most of these therapeutic agents. These products are widely recognized in the pharmaceutical industry for their broad structural diversity as well as their wide range of pharmacological activities. Euphorbiaceae is one of the important families with significant pharmacological activities, of which many species has been used traditionally for the treatment of various ailments. Breynia retusa belongs to the family Euphorbiaceae is used to cure ailments like body pain, skin inflammation, hyperglycaemia, diarrhoea, dysentery and toothache. Flowers and young leaves of B. retusa are cooked and eaten, roots are used for meningitis. The juice of the stem is used in conjunctivtis and leaves as poultice to hasten suppuration. Based on the strong evidences of traditional uses of Breynia retusa, the present study was focused on neutraceuticals evaluation of the species with special reference to oxidative stress and diabetes. Both leaves and stem of B. retusa were extracted with different solvents and analyzed for radical scavenging ability wherein ABTS.+ (8396.95±1529.01 µM TEAC/g extract), phosphomolybdenum (17.34±0.08 g AAE/100 g extract) and FRAP (6075.66±414.28 µM Fe (II) E/mg extract) assays showed good radical scavenging activity in stem. Furthermore, leaf extracts showed good radical inhibition in DPPH (2.4 µg/mL), metal ion (27.44±0.09 mg EDTAE/g extract) scavenging methods. The α-amylase and α-glucosidase inhibitors are currently used for diabetic treatment as oral hypoglycemic agents. The inhibitory effects of the B. retusa leaf and stem ethyl acetate extracts showed good inhibition on α-amylase (96.25% and 95.69 respectively) and α-glucosidase (54.50% and 50.87% respectively) enzymes compared to standard acarbose. The proximate composition analysis of B. retusa leaves contains higher amount of total carbohydrates (14.08 g Glucose equivalents/100 g sample), ash (19.04 %) and crude fibre (0.52 %). The examination of mineral profile explored that the leaves was rich in calcium (1891 ppm), sulphur (1406 ppm), copper (2600 ppm) and magnesium (778 ppm). Leaves sample revealed very minimal amount of anti-nutrient contents like trypsin (14.08±0.03 TIU/mg protein) and tannin (0.011±0.001 mg TAE/g sample). The low anti nutritional factors may not pose any serious nutritional problems when these leaves are consumed. In conclusion, it is very clear that dietary compounds from B. retusa are suitable and promising for the development of safe food products and natural additives. Based on the studies, it may be concluded that nutritional composition, antioxidant and anti-diabetic activities this species can be used as future therapeutic medicine.

Keywords: Breynia retusa, nutraceuticals, antioxidant, anti diabetic

Procedia PDF Downloads 306

Authors: ZhenlinJu, Christopher P. Vellano, RehanAkbani, Yiling Lu, Gordon B. Mills

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The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal characteristics, such as profound disruption of cell-cell junctions, loss of apical-basolateral polarity, and extensive reorganization of the actin cytoskeleton to induce cell motility and invasion. A hallmark of EMT is its capacity to promote metastasis, which is due in part to activation of several transcription factors and subsequent downregulation of E-cadherin. Unfortunately, current approaches have yet to uncover robust protein marker sets that can classify tumors as possessing strong EMT signatures. In this study, we utilize reverse phase protein array (RPPA) data and consensus clustering methods to successfully classify a subset of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tumors into an EMT protein signaling group (EMT group). The overall survival (OS) of patients in the EMT group is significantly worse than those in the other Hormone and PI3K/AKT signaling groups. In addition to a shrinkage and selection method for linear regression (LASSO), we applied training/test set and Monte Carlo resampling approaches to identify a set of protein markers that predicts the EMT status of CESC tumors. We fit a logistic model to these protein markers and developed a classifier, which was fixed in the training set and validated in the testing set. The classifier robustly predicted the EMT status of the testing set with an area under the curve (AUC) of 0.975 by Receiver Operating Characteristic (ROC) analysis. This method not only identifies a core set of proteins underlying an EMT signature in cervical cancer patients, but also provides a tool to examine protein predictors that drive molecular subtypes in other diseases.

Keywords: consensus clustering, TCGA CESC, Silhouette, Monte Carlo LASSO

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Authors: Muhammad Aasim, Mehmet Karataş, Fatih Erci, Şeyma Bakırcı, Ecenur Korkmaz, Burak Kahveci

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Water hyssop (Bacopa monnieri L. Wettst.) is an important medicinal aquatic/semi aquatic plant native to India where it is used in traditional medicinal system. The plant contains bioactive compounds mainly Bacosides which are the main ingridient of commercial drug available as memory enhancer tonic. The local name of water hyssop is Brahmi and brahmi based drugs are available against for curing chronic diseases and disorders Alzheimer’s disease, anxiety, asthma, cancer, mental illness, respiratory ailments, and stomach ulcers. The plant is not a cultivated plant and collection of plant from nature make palnt threatened to endangered. On the other hand, low seed viability and availability make it difficult to propagate plant through traditional techniques. In recent years, plant tissue culture techniques have been employed to propagate plant for its conservation and production for continuous availability of secondary metabolites. On the other hand, application of nanoparticles has been reported for increasing biomass, in vitro regeneration and secondary metabolites production. In this study, silver nanoparticles (AgNPs) were applied at the rate of 2, 4, 6, 8 and 10 ppm to Murashihe and Skoog (MS) medium supplemented with 1.0 mg/l Benzylaminopurine (BAP), 3.0% sucrose and 0.7% agar. Leaf explants of water hyssop were cultured on AgNPs containing medium. Shoot induction from leaf explants were relatively slow compared to medium without AgNPs. Multiple shoot induction was recorded after 3-4 weeks of culture comapred to control that occured within 10 days. Regenerated shoots were rooted successfully on MS medium supplemented with 1.0 mg/l IBA and acclimatized in the aquariums for further studies.

Keywords: Water hyssop, Silver nanoparticles, In vitro, Regeneration, Secondary metabolites

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Authors: Yasuyuki Takahashi, Hirotaka Shimada, Kyoko Saito

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Bone scintigraphy is widely used as a screening tool for bone metastases. However, the 180 to 240 minutes (min) waiting time after the intravenous (i.v.) injection of the tracer is both long and tiresome. To solve this shortcoming, a bone scan with a shorter waiting time is needed. In this study, we applied the Maximum Intensity Projection (MIP) and triple energy window (TEW) scatter correction to a whole body bone SPECT (Merged SPECT) and investigated shortening the waiting time. Methods: In a preliminary phantom study, hot gels of 99mTc-HMDP were inserted into sets of rods with diameters ranging from 4 to 19 mm. Each rod set covered a sector of a cylindrical phantom. The activity concentration of all rods was 2.5 times that of the background in the cylindrical body of the phantom. In the human study, SPECT images were obtained from chest to abdomen at 30 to 180 min after 99mTc- hydroxymethylene diphosphonate (HMDP) injection of healthy volunteers. For both studies, MIP images were reconstructed. Planar whole body images of the patients were also obtained. These were acquired at 200 min. The image quality of the SPECT and the planar images was compared. Additionally, 36 patients with breast cancer were scanned in the same way. The delectability of uptake regions (metastases) was compared visually. Results: In the phantom study, a 4 mm size hot gel was difficult to depict on the conventional SPECT, but MIP images could recognize it clearly. For both the healthy volunteers and the clinical patients, the accumulation of 99mTc-HMDP in the SPECT was good as early as 90 min. All findings of both image sets were in agreement. Conclusion: In phantoms, images from MIP with TEW scatter correction could detect all rods down to those with a diameter of 4 mm. In patients, MIP reconstruction with TEW scatter correction could improve the detectability of hot lesions. In addition, the time between injection and imaging could be shortened from that conventionally used for whole body scans.

Keywords: merged SPECT, MIP, TEW scatter correction, 99mTc-HMDP

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Authors: Aghaei Amirkhizi Navideh, Sadjadi Soodeh Sadat, Moghaddam Banaem Leila, Athari Allaf Mitra, Johari Daha Fariba

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Dendrimers are good candidates for preparing metal nanoparticles because they can structurally and chemically well-defined templates and robust stabilizers. Poly amidoamine (PAMAM) dendrimer-based multifunctional cancer therapeutic conjugates have been designed and synthesized in pharmaceutical industry. In addition, encapsulated nanoparticle surfaces are accessible to substrates so that catalytic reactions can be carried out. For preparation of dendimer-metal nanocomposite, a dendrimer solution containing an average of 55 Yb+3 ions per dendrimer was prepared. Prior to reduction, the pH of this solution was adjusted to 7.5 using NaOH. NaBH4 was used to reduce the dendrimer-encapsulated Yb+3 to the zerovalent metal. The pH of the resulting solution was then adjusted to 3, using HClO4, to decompose excess BH4-. The UV-Vis absorption spectra of the mixture were recorded to ensure the formation of Yb-G5-NH2 complex. High-resolution electron microscopy (HRTEM) and size distribution results provide additional information about dendimer-metal nanocomposite shape, size, and size distribution of the particles. The resulting mixture was irradiated in Tehran Research Reactor 2h and neutron fluxes were 3×1011 n/cm2.Sec and the specific activity was 7MBq. Radiochemical and chemical and radionuclide quality control testes were carried. Gamma Spectroscopy and High-performance Liquid Chromatography HPLC, Thin-Layer Chromatography TLC were recorded. The injection of resulting solution to solid tumor in mice shows that it could be resized the tumor. The studies about solid tumors and nano composites show that ytterbium encapsulated-dendrimer radiopharmaceutical could be introduced as a new therapeutic for the treatment of solid tumors.

Keywords: nano-radio pharmaceutical, ytterbium, PAMAM, dendrimers

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Authors: Hye Jin Choi, Mirim Jin, Jeong June Choi

Abstract:

Green tea, which is one of the most popular of tea, contains various ingredients that help health. Epigallocatechin gallate (EGCG) is one of the main active polyphenolic compound possessing diverse biologically beneficial effects such as anti-oxidation, anti-cancer founding in green tea. This study was performed to investigate the anti-diabetic effect of high-purity EGCG ( > 98%) in a spontaneous diabetic mellitus animal model, db/db mouse. Four-week-old male db/db mice, which was induced to diabetic mellitus by the high-fat diet, were orally administered with high-purity EGCG (10, 50 and 100 mg/kg) for 4 weeks. Daily weight and diet efficiency were examined, and blood glucose level was assessed once a week. After 4 weeks of EGCG administration, fasting blood glucose level was measured. Then, the mice were sacrificed and total abdominal fat was sampled to examine the change in fat weight. Plasma was separated from the blood and the levels of aspartate amino-transferase (ALT) and alanine amino-transferase (AST) were investigated. As results, blood glucose and body weight were significantly decreased by EGCG treatment compared to the control group. Also, the amount of abdominal fat was down-regulated by EGCG. However, ALT and AST levels, which are indicators of liver function, were similar to those of control group. Taken together, our study suggests that high purity EGCG is capable of treating diabetes mellitus based in db / db mice with safety and has a potent to develop a therapeutics for metabolic disorders. This work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry (IPET) through High Value-added Food Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (317034-03-2-HD030)

Keywords: anti-diabetic effect, db/db mouse, diabetes mellitus, green tea, epigallocatechin gallate

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Authors: Ebenezer O. Ige, Funmilayo H. Oyelami, Joshua Olutayo-Irheren, Joseph T. Okunlola

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Hyperthermia therapy is an adjuvant procedure during which perfused body tissues is subjected to elevated range of temperature in bid to achieve improved drug potency and efficacy of cancer treatment. While a selected class of hyperthermia techniques is shouldered on the thermal radiations derived from single-sourced electro-radiation measures, there are deliberations on conjugating dual radiation field sources in an attempt to improve the delivery of therapy procedure. This paper numerically explores the thermal effectiveness of combined infrared hyperemia having nanoparticle recirculation in the vicinity of imposed magnetic field on subcutaneous strata of a model lesion as ablation scheme. An elaborate Spectral relaxation method (SRM) was formulated to handle equation of coupled momentum and thermal equilibrium in the blood-perfused tissue domain of a spongy fibrous tissue. Thermal diffusion regimes in the presence of external magnetic field imposition were described leveraging on the renowned Roseland diffusion approximation to delineate the impact of radiative flux within the computational domain. The contribution of tissue sponginess was examined using mechanics of pore-scale porosity over a selected of clinical informed scenarios. Our observations showed for a substantial depth of spongy lesion, magnetic field architecture constitute the control regimes of hemodynamics in the blood-tissue interface while facilitating thermal transport across the depth of the model lesion. This parameter-indicator could be utilized to control the dispensing of hyperthermia treatment in intravenous perfused tissue.

Keywords: spectra relaxation scheme, thermal equilibrium, Roseland diffusion approximation, hyperthermia therapy

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