Search results for: poor outcome of delayed breast cancer treatment
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 13453

Search results for: poor outcome of delayed breast cancer treatment

11893 Psycholinguistic Analysis on Stuttering Treatment through Systemic Functional Grammar in Tom Hooper’s The King’s Speech

Authors: Nurvita Wijayanti

Abstract:

The movie titled The King’s Speech is based on a true story telling an English king suffers from stuttering and how he gets the treatment from the therapist, so that he can reduce the high frequency on stuttering. The treatment uses the unique approach implying the linguistic principles. This study shows how the language works significantly in order to treat the stuttering sufferer using psychological approach. Therefore, the linguistic study is done to analyze the treatment activity. Halliday’s Systemic Functional Grammar is used as the main approach in this study along with qualitative descriptive method. The study finds that the therapist though using the orthodox approach applies the psycholinguistic method to overcome the king’s stuttering.

Keywords: psycholinguistics, stuttering, systemic functional grammar, treatment

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11892 Signal Processing of Barkhausen Noise Signal for Assessment of Increasing Down Feed in Surface Ground Components with Poor Micro-Magnetic Response

Authors: Tanmaya Kumar Dash, Tarun Karamshetty, Soumitra Paul

Abstract:

The Barkhausen Noise Analysis (BNA) technique has been utilized to assess surface integrity of steels. But the BNA technique is not very successful in evaluating surface integrity of ground steels that exhibit poor micro-magnetic response. A new approach has been proposed for the processing of BN signal with Fast Fourier transforms while Wavelet transforms has been used to remove noise from the BN signal, with judicious choice of the ‘threshold’ value, when the micro-magnetic response of the work material is poor. In the present study, the effect of down feed induced upon conventional plunge surface grinding of hardened bearing steel has been investigated along with an ultrasonically cleaned, wet polished and a sample ground with spark out technique for benchmarking. Moreover, the FFT analysis has been established, at different sets of applied voltages and applied frequency and the pattern of the BN signal in the frequency domain is analyzed. The study also depicts the wavelet transforms technique with different levels of decomposition and different mother wavelets, which has been used to reduce the noise value in BN signal of materials with poor micro-magnetic response, in order to standardize the procedure for all BN signals depending on the frequency of the applied voltage.

Keywords: barkhausen noise analysis, grinding, magnetic properties, signal processing, micro-magnetic response

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11891 Development of Visual Working Memory Precision: A Cross-Sectional Study of Simultaneously Delayed Responses Paradigm

Authors: Yao Fu, Xingli Zhang, Jiannong Shi

Abstract:

Visual working memory (VWM) capacity is the ability to maintain and manipulate short-term information which is not currently available. It is well known for its significance to form the basis of numerous cognitive abilities and its limitation in holding information. VWM span, the most popular measurable indicator, is found to reach the adult level (3-4 items) around 12-13 years’ old, while less is known about the precision development of the VWM capacity. By using simultaneously delayed responses paradigm, the present study investigates the development of VWM precision among 6-18-year-old children and young adults, besides its possible relationships with fluid intelligence and span. Results showed that precision and span both increased with age, and precision reached the maximum in 16-17 age-range. Moreover, when remembering 3 simultaneously presented items, the probability of remembering target item correlated with fluid intelligence and the probability of wrap errors (misbinding target and non-target items) correlated with age. When remembering more items, children had worse performance than adults due to their wrap errors. Compared to span, VWM precision was effective predictor of intelligence even after controlling for age. These results suggest that unlike VWM span, precision developed in a slow, yet longer fashion. Moreover, decreasing probability of wrap errors might be the main reason for the development of precision. Last, precision correlated more closely with intelligence than span in childhood and adolescence, which might be caused by the probability of remembering target item.

Keywords: fluid intelligence, precision, visual working memory, wrap errors

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11890 Readout Development of a LGAD-based Hybrid Detector for Microdosimetry (HDM)

Authors: Pierobon Enrico, Missiaggia Marta, Castelluzzo Michele, Tommasino Francesco, Ricci Leonardo, Scifoni Emanuele, Vincezo Monaco, Boscardin Maurizio, La Tessa Chiara

Abstract:

Clinical outcomes collected over the past three decades have suggested that ion therapy has the potential to be a treatment modality superior to conventional radiation for several types of cancer, including recurrences, as well as for other diseases. Although the results have been encouraging, numerous treatment uncertainties remain a major obstacle to the full exploitation of particle radiotherapy. To overcome therapy uncertainties optimizing treatment outcome, the best possible radiation quality description is of paramount importance linking radiation physical dose to biological effects. Microdosimetry was developed as a tool to improve the description of radiation quality. By recording the energy deposition at the micrometric scale (the typical size of a cell nucleus), this approach takes into account the non-deterministic nature of atomic and nuclear processes and creates a direct link between the dose deposited by radiation and the biological effect induced. Microdosimeters measure the spectrum of lineal energy y, defined as the energy deposition in the detector divided by most probable track length travelled by radiation. The latter is provided by the so-called “Mean Chord Length” (MCL) approximation, and it is related to the detector geometry. To improve the characterization of the radiation field quality, we define a new quantity replacing the MCL with the actual particle track length inside the microdosimeter. In order to measure this new quantity, we propose a two-stage detector consisting of a commercial Tissue Equivalent Proportional Counter (TEPC) and 4 layers of Low Gain Avalanche Detectors (LGADs) strips. The TEPC detector records the energy deposition in a region equivalent to 2 um of tissue, while the LGADs are very suitable for particle tracking because of the thickness thinnable down to tens of micrometers and fast response to ionizing radiation. The concept of HDM has been investigated and validated with Monte Carlo simulations. Currently, a dedicated readout is under development. This two stages detector will require two different systems to join complementary information for each event: energy deposition in the TEPC and respective track length recorded by LGADs tracker. This challenge is being addressed by implementing SoC (System on Chip) technology, relying on Field Programmable Gated Arrays (FPGAs) based on the Zynq architecture. TEPC readout consists of three different signal amplification legs and is carried out thanks to 3 ADCs mounted on a FPGA board. LGADs activated strip signal is processed thanks to dedicated chips, and finally, the activated strip is stored relying again on FPGA-based solutions. In this work, we will provide a detailed description of HDM geometry and the SoC solutions that we are implementing for the readout.

Keywords: particle tracking, ion therapy, low gain avalanche diode, tissue equivalent proportional counter, microdosimetry

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11889 HKIE Accreditation: A Comparative Study on the Old and New Criteria

Authors: Peter P. K. Chiu

Abstract:

This paper reports a comparative study of new and old criteria for the professional accreditation of programme by the Hong Kong Institution of Engineers (HKIE). The major change in the criteria is the adoption of the outcome-based accreditation criteria and the use of measurement of attainment of outcomes which is very different from what academic did in the past. This has imposed a lot of difficulty for people in preparation for such exercise. Through this comparative study, the major difference between the two criteria is identified and a methodology is devised to help the academic to handle the issues due to the adoption of the new criteria. Thus it saves a lot of efforts.

Keywords: Hong Kong institution of engineers, outcome-based accreditation, Sydney accord, Washington accord

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11888 Azadirachta indica Derived Protein Encapsulated Novel Guar Gum Nanocapsules against Colon Cancer

Authors: Suman Chaudhary, Rupinder K. Kanwar, Jagat R. Kanwar

Abstract:

Azadirachta indica, also known as Neem belonging to the mahogany family is actively gaining interest in the era of modern day medicine due to its extensive applications in homeopathic medicine such as Ayurveda and Unani. More than 140 phytochemicals have been extracted from neem leaves, seed, bark and flowers for agro-medicinal applications. Among the various components, neem leaf protein (NLP) is currently the most investigated active ingredient, due to its immunomodulatory activities against tumor growth. However, these therapeutic ingredients of neem are susceptible to degradation and cannot withstand the drastic pH changes under physiological environment, and therefore, there is an urgent need of an alternative strategy such as a nano-delivery system to exploit its medicinal benefits. This study hypothesizes that guar gum (GG) derived biodegradable nano-carrier based encapsulation of NLP will improve its stability, specificity and sensitivity, thus facilitating targeted anti-cancer therapeutics. GG is a galactomannan derived from the endosperm of the guar beans seeds. Synthesis of guar nanocapsules (NCs) was performed using nanoprecipitation technique where the GG was encapsulated with NLP. Preliminary experiments conducted to characterize the NCs confirmed spherical morphology with a narrow size distribution of 30-40 nm. Differential scanning colorimetric analysis (DSC) validated the stability of these NCs even at a temperature range of 50-60°C which was well within the physiological and storage conditions. Thermogravimetric (TGA) analysis indicated high decomposition temperature of these NCs ranging upto 350°C. Additionally, Fourier Transform Infrared spectroscopy (FTIR) and the SDS-PAGE data acquired confirmed the successful encapsulation of NLP in the NCs. The anti-cancerous therapeutic property of this NC was tested on colon cancer cells (caco-2) as they are one of the most prevalent form of cancer. These NCs (both NLP loaded and void) were also tested on human intestinal epithelial cells (FHs 74) cells to evaluate their effect on normal cells. Cytotoxicity evaluation of the NCs in the cell lines confirmed that the IC50 for NLP in FHs 74 cells was ~2 fold higher than in caco-2 cells, indicating that this nanoformulation system possessed biocompatible anti-cancerous properties Immunoconfocal microscopy analysis confirmed the time dependent internalization of the NCs within 6h. Recent findings performed using Annexin V and PI staining indicated a significant increase (p ≤ 0.001) in the early and late apoptotic cell population when treated with the NCs signifying the role of NLP in inducing apoptosis in caco-2 cells. This was further validated using Western blot, Polymerase chain reaction (PCR) and Fluorescence activated cell sorter (FACS) aided protein expressional analysis which presented a downregulation of survivin, an anti-apoptotic cell marker and upregulation of Bax/Bcl-2 ratio (pro-apoptotic indicator). Further, both the NLP NC and unencapsulated NLP treatment destabilized the mitochondrial membrane potential subsequently facilitating the release of the pro-apoptotic caspase cascade initiator, cytochrome-c. Future studies will be focused towards granting specificity to these NCs towards cancer cells, along with a comprehensive analysis of the anti-cancer potential of this naturally occurring compound in different cancer and in vivo animal models, will validate the clinical application of this unprecedented protein therapeutic.

Keywords: anti-tumor, guar gum, nanocapsules, neem leaf protein

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11887 Intraventricular Hemorrhage Caused by Subarachnoid Hemorrhage; When Time Is Life

Authors: Devieta Romadhon Saendardy

Abstract:

Introduction: The case of aneurysmal subarachnoid hemorrhage (SAH) associated with intraventricular hemorrhage (IVH) in many way. In general, the anterior communicating artery and posterior circulation aneurysms cause Intraventricular Hemorrhage. The development of intraventricular hemorrhage (IVH) in aneurysmal subarachnoid hemorrhage (aSAH) is linked with higher mortality and poor neurological recovery. Case: This case report presents a 51-year-old female patient who developed IVH following SAH. The patient's Glasgow Coma Scale score was 14, the patient has a severe headache, and there were right extremity hemipharese neurological deficits. A non-contrast head CT scan revealed a massive intraventricular haemorrhage. In an hour, the patient got her headache and pharese worse. Discussion: Intraventricular hemorrhage is a serious complication of subarachnoid hemorrhage, necessitating prompt recognition and management. This case highlights the importance of a time management, medical management and surgical intervention to optimize outcomes in patients with intraventricular hemorrhage caused by subarachnoid hemorrhage. Placement of a shunt system improves clinical outcome in intraventricular hemorrhage.

Keywords: Intraventricular hemorrhage, subarachnoid hemorrhage, shunt, time

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11886 Awareness regarding Radiation Protection among the Technicians Practicing in Bharatpur, Chitwan, Nepal

Authors: Jayanti Gyawali, Deepak Adhikari, Mukesh Mallik, Sanjay Sah

Abstract:

Radiation is defined as an emission or transmission of energy in form of waves or particles through space or material medium. The major imaging tools used in diagnostic radiology is based on the use of ionizing radiation. A cross-sectional study was carried out during July- August, 2015 among technicians in 15 different hospitals of Bharatpur, Chitwan, Nepal to assess awareness regarding radiation protection and their current practice. The researcher was directly engaged for data collection using self-administered semi-structured questionnaire. The findings of the study are presented in socio-demographic characteristics of respondents, current practice of respondents and knowledge regarding radiation protection. The result of this study demonstrated that despite the importance of radiation and its consequent hazards, the level of knowledge among technicians is only 60.23% and their current practice is 76.84%. The difference in the mean score of knowledge and practice might have resulted due to technicians’s regular work and lack of updates. The study also revealed that there is no significant (p>0.05) difference in knowledge level of technicians practicing in different hospitals. But the mean difference in practice scores of different hospital is significant (p<0.05) i.e. i.e. the cancer hospital with large volumes of regular radiological cases and radiation therapies for cancer treatment has better practice in comparison to other hospitals. The deficiency in knowledge of technicians might alter the expected benefits, compared to the risk involved, and can cause erroneous medical diagnosis and radiation hazard. Therefore, this study emphasizes the need for all technicians to update themselves with the appropriate knowledge and current practice about ionizing and non-ionizing radiation.

Keywords: technicians, knowledge, Nepal, radiation

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11885 Poverty Eradication Program in Malaysia

Authors: Ibrahim Mamat, Wan Mohd Zaifurin Wan Nawang

Abstract:

Malaysia's poverty eradication program is a long-term plan that was initially implemented by the government after the riots of the races on May 13, 1969. The incident broke out due to the huge economic gap between the majority of Malaysians,Malays and non-Malays minorities. As a result of the event, the government drafted the New Economic Policy(NEP) in 1970 to reduce the differences in economic status among races in Malaysia. At the end of this policy period (NEP) in 1990, the incidence of poverty in Malaysia was around 6.5 per cent. The incidence of poverty in Malaysia continued to decline to 0.6 per cent (2014) through some other policy after the NEP. The decline in poverty has been the result of the government's efforts to implement the New Economic Policy (1970-1990), National Development Policy (1991-2000), NationalVision Policy (2001-2010), and National Transformation Policy (2011-2020).This article also explains the meaning, concepts and measurements of poverty in order to identify the Poverty Level and measure the Poverty Index using various dimensions. This explanation is very important for a country like Malaysia who has some people living below the poverty line. In such a context, an effective poverty eradication policy can benefit the poor.Consequently, this article examines the continuing involvement of the government and non-governmental organizations through the empowerment program of the hardcore poor to change their lifestyle and culture as well as the vicious circle of poverty is indispensable to ensure that poverty eradication programs are in line with current economic and social changes. In addition, the involvement of non-governmental organizations and the State Islamic Religious Council to provide assistance to the poor is appropriate as the institution has its own distinctive interpretation of poverty to determine the type of assistance, criteria and so on to enable the rights of the poor to be ensured and protected.

Keywords: economic policy, poor, poverty eradication, poverty program

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11884 Medicinal Plants Used by Moroccan People in the Management of Diabetes and Hypertension

Authors: Alami Ilyass, Kharchoufa Loubna, Alachouri Mostafa

Abstract:

Cardiovascular disease (CDV) remains the major cause of morbidity; mortality and disability throughout the world. The ethnopharmcological and ethnobotanical studies are the paramount importance to set a high value on phytogenetic resources and to address health problems of some communities; especially poor peoples. Our work presents an analysis of published data from studies, that have been undertaken, in Morocco, by different seeker teams in separately areas during the last decades. Objectives: Evaluate and identify medicinal plants used for cardiovascular treatment by Moroccan people. Methodology: All these studies have the same approaches ; they were conducted by interviewing people suffering from diabetes. We use Factorial Analysis (FA) and principal Components analysis (PCA) to analyse the aggregated data from the different studies. Results: globally; 95 plants species were listed; all these plant were used empirically by Moroccan society for treating cardiovascular problems. These plants were divided in to 42 families and 87 genus. The lamiaceae; asteraceae; Apiaceae and poaceae are the botanical families with high number of plant species. Coclusion: Traditional medecine has been widely used for treatment of cardiovascular problems and it has been recognized as an interesting alternative to conventional medicine.

Keywords: cardiovascular, ethnobotanical, medicinal plants, Morocco

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11883 Domestic Wastewater Treatment by Microalgae – Removal of Nitrogen

Authors: A. Siham Dehmani, B. Djamal Zerrouki

Abstract:

Domestic wastewater contains high concentrations of nitrogen, which can affect public health and cause harmful ecological impacts. The potential of microalgae as a source of renewable energy based on wastewater has received increasing interest worldwide in recent decades. The microalgae cultivation in wastewater has two advantages: wastewater treatment and algal biomass production. Our work aimed to remove nitrogen from municipal wastewater. Wastewater samples were taken from the wastewater treatment station located in Ouargla and used as a medium for the cultivation of chlorella microalgae strains inside a photobioreactor. Analysis of different parameters was done every 2 days along the period of the cultivation (10 days). The average removal efficiencies of nitrogen were maintained at 95%. Our results show the potential of integrating nutrient removal from wastewater by microalgae as a secondary wastewater treatment processes.

Keywords: biomass, microalgae, treatment, wastewater

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11882 The Impact of Treatment of Latent Tuberculosis on the Incidence: The Case of Algeria

Authors: Schehrazad Selmane

Abstract:

We present a deterministic model which describes the dynamics of tuberculosis in Algerian population where the vaccination program with BCG is in place since 1969 and where the WHO recommendations regarding the DOTS (directly observed treatment, short course) strategy are in application. The impact of an intervention program, targeting recently infected people among all close contacts of active cases and their treatment to prevent endogenous reactivation, on the incidence of tuberculosis, is investigated. We showed that a widespread treatment of latently infected individuals for some years is recommended to shift from higher to lower equilibrium state and thereafter relaxation is recommended.

Keywords: deterministic model, reproduction number, stability, tuberculosis

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11881 To Corelate Thyroid Dysfunction in Pregnancy with Preterm Labor

Authors: Pushp Lata Sankhwar

Abstract:

INTRODUCTION: Maternal Hypothyroidism is the most frequent endocrine disorder in pregnancy and varies from 2.5% in the west to 11.0% in India. Maternal Hypothyroidism can have detrimental maternal effects like increased risk of preterm labor, PPROM leading to increased maternal morbidity and also on the neonate in the form of prematurity and its complications, prolonged hospital stay, neurological developmental problems, delayed milestones and mental retardation etc. Henceforth, the study was planned to evaluate the role of Hypothyroidism in preterm labor and its effect on neonates. AIMS AND OBJECTIVES: To Correlate Overt Hypothyroidism, Subclinical Hypothyroidism and Isolated Hypothyroxinemia With Preterm Labor and the neonatal outcome. Material and Methods: A case-control study of singleton pregnancy was performed over a year, in which a total of 500 patients presenting in the emergency with preterm labor were enrolled. The thyroid profile of these patients was sent at the time of admission, on the basis of which they were divided into Cases – Hypothyroidic mothers and Controls – Euthyroid mothers. The cases were further divided into subclinical, overt Hypothyroidism and isolated hypothyroxinemia. The neonatal outcome of these groups was also compared on the basis of the incidence and severity of neonatal morbidity, neonatal respiratory distress, the incidence of neonatal Hypothyroidism and early complications. The feto-maternal data was collected and analysed. RESULTS: In the study, a total of 500 antenatal patients with a history of preterm labor were enrolled, out of which 67 (13.8%) patients were found to be hypothyroid. The majority of the mothers had Subclinical Hypothyroidism (12.2%), followed by Overt Hypothyroidism seen in 1% of the mothers and isolated hypothyroxinemia in 0.6% of cases. The neonates of hypothyroid mothers had higher levels of cord blood TSH, and the mean cord blood TSH levels were highest in the case of neonates of mothers with Overt Hypothyroidism. The need for resuscitation of the neonates at the time of birth was higher in the case of neonates of hypothyroid mothers, especially with Subclinical Hypothyroidism. Also, it was found that the requirement of oxygen therapy in the form of oxygen by nasal prongs, oxygen by a hood, CPAP, CPAP along with surfactant therapy and mechanical ventilation along with surfactant therapy was significantly higher in the case of neonates of hypothyroid mothers. CONCLUSION: The results of our study imply that uncontrolled and untreated maternal Hypothyroidism may also lead to preterm delivery. The neonates of mothers with Hypothyroidism have higher cord blood TSH levels. The study also shows that there is an increased incidence and severity of respiratory distress in the neonates of hypothyroid mothers with untreated subclinical Hypothyroidism. Hence, we propose that routine screening for thyroid dysfunction in pregnant women should be done to prevent thyroid-related feto-maternal complications.

Keywords: high-risk pregnancy, thyroid, dysfunction, hypothyroidism, Preterm labor

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11880 A Constructed Wetland as a Reliable Method for Grey Wastewater Treatment in Rwanda

Authors: Hussein Bizimana, Osman Sönmez

Abstract:

Constructed wetlands are current the most widely recognized waste water treatment option, especially in developing countries where they have the potential for improving water quality and creating valuable wildlife habitat in ecosystem with treatment requirement relatively simple for operation and maintenance cost. Lack of grey waste water treatment facilities in Kigali İnstitute of Science and Technology in Rwanda, causes pollution in the surrounding localities of Rugunga sector, where already a problem of poor sanitation is found. In order to treat grey water produced at Kigali İnstitute of Science and Technology, with high BOD concentration, high nutrients concentration and high alkalinity; a Horizontal Sub-surface Flow pilot-scale constructed wetland was designed and can operate in Kigali İnstitute of Science and Technology. The study was carried out in a sedimentation tank of 5.5 m x 1.42 m x 1.2 m deep and a Horizontal Sub-surface constructed wetland of 4.5 m x 2.5 m x 1.42 m deep. The grey waste water flow rate of 2.5 m3/d flew through vegetated wetland and sandy pilot plant. The filter media consisted of 0.6 to 2 mm of coarse sand, 0.00003472 m/s of hydraulic conductivity and cattails (Typha latifolia spp) were used as plants species. The effluent flow rate of the plant is designed to be 1.5 m3/ day and the retention time will be 24 hrs. 72% to 79% of BOD, COD, and TSS removals are estimated to be achieved, while the nutrients (Nitrogen and Phosphate) removal is estimated to be in the range of 34% to 53%. Every effluent characteristic will meet exactly the Rwanda Utility Regulatory Agency guidelines primarily because the retention time allowed is enough to make the reduction of contaminants within effluent raw waste water. Treated water reuse system was developed where water will be used in the campus irrigation system again.

Keywords: constructed wetlands, hydraulic conductivity, grey waste water, cattails

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11879 Utility of Routine Colonoscopy in Acute Diverticulitis

Authors: Naya Masood, Russell Hodgson, Mark Tacey

Abstract:

Purpose: Patients with acute diverticulitis (AD) have an increased risk of underlying colorectal cancer (CRC); however, those with uncomplicated AD may have the same underlying population risk. This study informs on an Australian AD population who were not routinely offered colonoscopic follow-up. Methods: A 2-year (July 2016 – June 2018) retrospective study of patients admitted with CT-confirmed acute diverticulitis was conducted. CT findings were categorised as ‘complicated’ and ‘uncomplicated’ and were correlated with the detection of cancer in subsequent colonoscopy or follow-up. Results: 67.7% (n=292) of 431 patients were seen to have had complicated AD on an abdominopelvic CT scan. Patients were complicated most commonly due to bowel wall thickening reported on CT (90.4%), perforation (20.2%), or an abscess (12%). Follow-up colonoscopic evaluation was conducted in 52.9% (n=228) of total cases of AD, out of which 156 suffered complicated AD and the rest uncomplicated. None of the uncomplicated AD patients in our cohort were found to have CRC. Of those with complicated AD, six were found to have CRC. Conclusion: The only CRC diagnoses were made in patients with complicated AD. Despite available evidence, a significant proportion of uncomplicated AD patients were still undergoing colonoscopy. There is scope to further safely decrease the number of colonoscopies performed in AD patients.

Keywords: acute diverticulitis, colonoscopy, colorectal cancer, advanced adenoma, complicated diverticulitis

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11878 Abnormal Pap Smear Detection by Application of Revised Bethesda System in Commercial Sex Workers and a Control Group: A Comparative Study

Authors: Priyanka Manghani, Manthan Patel, Rahul Peddawad

Abstract:

Cervical Cancer is a major public health hurdle in the area of women’s health. The most common cause of Cervical Cancer is the Human Papilloma Virus (HPV). Human papilloma virus has various genotypes, with HPV 16 and HPV 18 being the major etiological factor causing carcinoma of the Cervix. Early screening and detection by Papanicolaou Smears (PAP) is an effective method for identifying premalignant and malignant lesions. In case of existing pre- malignant lesions /cervical dysplasia’s found with HPV 16 or 18, appropriate follow up can be done to prevent it from developing into a neoplasm. Aims and Objectives: Primary Aim; To study various abnormal cervical cytology reports as detected by Pap Smear Tests, using the Bethesda System in women at a Tertiary Care Hospital. Secondary Aim; To discuss the importance of Pap smear in Cervical Cancer Screening Program. Materials and Methods: Our study is a prospective study, based on 101 women who attended the Out-patient department of Obstetrics and Gynecology at a tertiary care hospital in age group 20-40 years with chief complaints of white/foul vaginal discharge, post-coital Bleeding, low back pain, irregular menstruation, etc. 60 women, who were tested, of the total no of women, were commercial sex workers, thus being a high-risk group for HPV infection. All women underwent conventional cytology. For all the abnormal smears, further cervical biopsies were done, and the final diagnosis was done on the basis of histopathology (gold standard). Results: In all these patients, 16 patients presented with normal smears out of which 2 belonged to the category of commercial sex workers (3.33%) and 14 being from the normal/control group (34.15%). 44 women presented with inflammatory smears out of which 30 were commercial sex workers (50%) and 14 from the control Group (34.15%). A total of 11 women presented with infectious etiology with 6 being commercial sex workers (10%) and 5 (12.2%) being in the control group. A total of 8 patients presented with low-grade squamous intra epithelial lesion (LSIL) with 7 (11.7%) being commercial sex workers and 1(2.44%) patient belonging to the control group. A Total of 7 patients presented with high-grade squamous intraepithelial lesion (HSIL) with 6 (10%) being commercial sex workers and 1 (2.44%) belonging to the control group. 9 patients in total presented with atypical squamous cells of undetermined significance (ASCUS) with 6(10%) being commercial sex workers and 3 (7.32%) belonging to the control group. Squamous cell carcinoma(SCC) presence was found only in 1(1.7%) commercial sex worker. Conclusion – We conclude that HSIL, LSIL, SCC and sexually related infections are comparatively more common in vulnerable groups such as sex workers due to a variety of factors such as multiple sexual partners and poor genital hygiene. Early screening and follow up interventions are highly needed for them along with Health education for risk factors and to emphasize on the importance of Pap smear screening.

Keywords: cervical cancer, papanicolaou (pap) smear, bethesda system, neoplasm

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11877 Evaluation on Estrogenic Effects of Diisononyl Adipate (DiNA) on MCF-7 Human Breast Cancer Cell Lines

Authors: Shih-cheng Li, Ming-Yi Chung, Mei-Lien Chen

Abstract:

Background: Plasticizers, such as phthalates and adipates, were substances added to a material that provided flexibility and durability to plastics such as polyvinyl chloride (PVC). Phthalates were generally recognized as an endocrine disrupter due to their estrogenic and anti-androgenic activities. Phthalates had the capacity to bind to estrogen receptors, and hence they might prolong menstrual cycles and increase the proportion of premature menopause. Recently, adipates such as di-2-ethylhexyl adipate (DEHA) and di-isononyl adipate (DiNA) had replaced phthalates and were now used for food packaging. Methods: MCF-7 cell lines were treated with di-2-ethylhexyl phthalate (DEHP), di- 2-ethylhexyl adipate (DEHA), or di-isononyl adipate (DiNA) (10-6 , 10-5 , and 10-4 mol/l), using 17β-estradiol (10-8 mol/l) as a positive control. After incubations of 24, 48, 72, and 96 hours, the cells were tested using the alamarBlue assay. Results: The alamarBlue assay revealed that cell proliferation significantly increased after treatments of DEHP and DEHA for 24 hours at a concentration of 10-6, 10-5, and 10-4 mol/l. After more than 48 hours, cell proliferations in DEHP at 10-6, 10-5, and 10-4 mol/l significantly decreased compared to the control group. Conclusions: The present study demonstrates that adipates, as well as phthalates, were capable of inducing cell proliferation. We further used MDA-MB-231 cell lines to confirm that the proliferation effect was generated through binding to estrogen receptors.

Keywords: MCF-7, phthalate, adipate, endocrine disrupter

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11876 The Impact of the COVID-19 Pandemic on the Nursing Workforce in Slovakia

Authors: Lukas Kober, Vladimir Littva, Vladimir Siska

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The pandemic has had a significant impact on our lives. One of the most affected professions is the nursing profession. Nurses are closest to the patient, spend the most time with him, support him, often replace the closest family members, and of course, are part of the whole treatment process. Current nurses have more competencies and roles than in the past. The healthcare system has reached a turning point, also in connection with the spreading Delta variant and the risk of the arrival of the third wave. The lack of nurses is a long-term problem, but it did not arise by itself. The reasons for the departure of nurses from the health care system are not only due to the increasing average age of nurses and midwives in Slovakia and their retirement. Thousands of nurses are leaving due to poor working conditions, low wages, and poor management of individual workplaces. We need to keep older nurses in the health care system, otherwise, we risk their early departure. The pandemic only exacerbates this situation, and the associated risks, such as occupational infections or enormous overload and exhaustion, only accelerate the exit from the profession. According to current data from the register of nurses and midwives, we canceled 772 registrations from January to September 2021, and 584 nurses requested the suspension of registration due to non-performance of the profession. During the same period, we registered only 240 new nurses graduate. We have had this significant disparity here for a long time. For the whole of 2020, we canceled 911 registrations and suspended 973 registrations. We registered a total of 389 graduates. Our system loses hundreds of graduates a year and loses experienced nurses with decades of experience who leave due to poor working conditions, wages and suffer from burnout. Such compensation should also be awarded to the families of health professionals who have lost their lives due to work and to COVID-19. These options can also be motivating for promising people interested in studying nursing, who can gradually replace the missing workforce. This purchase is supported by the KEGA project no. 015KU-4/2019.

Keywords: pandemic, COVID-19, nursing, nursing workforce, lack of nurses

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11875 Ellagic Acid Enhanced Apoptotic Radiosensitivity via G1 Cell Cycle Arrest and γ-H2AX Foci Formation in HeLa Cells in vitro

Authors: V. R. Ahire, A. Kumar, B. N. Pandey, K. P. Mishra, G. R. Kulkarni

Abstract:

Radiation therapy is an effective vital strategy used globally in the treatment of cervical cancer. However, radiation efficacy principally depends on the radiosensitivity of the tumor, and not all patient exhibit significant response to irradiation. A radiosensitive tumor is easier to cure than a radioresistant tumor which later advances to local recurrence and metastasis. Herbal polyphenols are gaining attention for exhibiting radiosensitization through various signaling. Current work focuses to study the radiosensitization effect of ellagic acid (EA), on HeLa cells. EA intermediated radiosensitization of HeLa cells was due to the induction γ-H2AX foci formation, G1 phase cell cycle arrest, and loss of reproductive potential, growth inhibition, drop in the mitochondrial membrane potential and protein expression studies that eventually induced apoptosis. Irradiation of HeLa in presence of EA (10 μM) to doses of 2 and 4 Gy γ-radiation produced marked tumor cytotoxicity. EA also demonstrated radio-protective effect on normal cell, NIH3T3 and aided recovery from the radiation damage. Our results advocate EA to be an effective adjuvant for improving cancer radiotherapy as it displays striking tumor cytotoxicity and reduced normal cell damage instigated by irradiation.

Keywords: apoptotic radiosensitivity, ellagic acid, mitochondrial potential, cell-cycle arrest

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11874 Dehydration of Residues from WTP for Application in Building Materials and Reuse of Water from the Waste Treatment: A Feasible Solution to Complete Treatment Systems

Authors: Marco Correa, Flavio Araujo, Paulo Scalize, Antonio Albuquerque

Abstract:

The increasing reduction of the volumes of surface water sources which supply most municipalities, as well as the continued rise of demand for treated water, combined with the disposal of effluents from washing of decanters and filters of the water treatment plants, generates a continuous search for correct environmentally solutions to these problems. The effluents generated by the water treatment industry need to be suitably processed for return to the environment or re-use. This article shows an alternative for the dehydration of sludge from the water treatment plants (WTP) and eventual disposal of sludge drained. Using the simple design methodology, we present a case study for a drainage in tanks geotextile, full-scale, which involve five sludge drainage tanks from WTP of the Rio Verde City. Aiming to the reutilization the water drained from the sludge and enabling its reuse both at the beginning of the treatment process at the WTP and in less noble services as for watering the gardens of the local town hall. The sludge will be used to production of building materials.

Keywords: re-use, residue, sustainable, water treatment plants, sludge

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11873 A Single Cell Omics Experiments as Tool for Benchmarking Bioinformatics Oncology Data Analysis Tools

Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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11872 Health Inequalities in the Global South: Identification of Poor People with Disabilities in Cambodia to Generate Access to Healthcare

Authors: Jamie Lee Harder

Abstract:

In the context of rapidly changing social and economic circumstances in the developing world, this paper analyses access to public healthcare for poor people with disabilities in Cambodia. Like other countries of South East Asia, Cambodia is developing at rapid pace. The historical past of Cambodia, however, has set former social policy structures to zero. This past forces Cambodia and its citizens to implement new public health policies to align with the needs of social care, healthcare, and urban planning. In this context, the role of people with disabilities (PwDs) is crucial as new developments should and can take into consideration their specific needs from the beginning onwards. This paper is based on qualitative research with expert interviews and focus group discussions in Cambodia. During the field work it became clear that the identification tool for the poorest households (HHs) does not count disability as a financial risk to fall into poverty neither when becoming sick nor because of higher health expenditures and/or lower income because of the disability. The social risk group of poor PwDs faces several barriers in accessing public healthcare. The urbanization, the socio-economic health status, and opportunities for education; all influence social status and have an impact on the health situation of these individuals. Cambodia has various difficulties with providing access to people with disabilities, mostly due to barriers regarding finances, geography, quality of care, poor knowledge about their rights and negative social and cultural beliefs. Shortened budgets and the lack of prioritizations lead to the need for reorientation of local communities, international and national non-governmental organizations and social policy. The poorest HHs are identified with a questionnaire, the IDPoor program, for which the Ministry of Planning is responsible. The identified HHs receive an ‘Equity Card’ which provides access free of charge to public healthcare centers and hospitals among other benefits. The dataset usually does not include information about the disability status. Four focus group discussions (FGD) with 28 participants showed various barriers in accessing public healthcare. These barriers go far beyond a missing ramp to access the healthcare center. The contents of the FGDs were ratified and repeated during the expert interviews with the local Ministries, NGOs, international organizations and private persons working in the field. The participants of the FGDs faced and continue to face high discrimination, low capacity to work and earn an own income, dependency on others and less social competence in their lives. When discussing their health situation, we identified, a huge difference between those who are identified and hold an Equity Card and those who do not. Participants reported high costs without IDPoor identification, positive experiences when going to the health center in terms of attitude and treatment, low satisfaction with specific capacities for treatments, negative rumors, and discrimination with the consequence of fear to seek treatment in many cases. The problem of accessing public healthcare by risk groups can be adapted to situations in other countries.

Keywords: access, disability, health, inequality, Cambodia

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11871 Optimization of Acid Treatments by Assessing Diversion Strategies in Carbonate and Sandstone Formations

Authors: Ragi Poyyara, Vijaya Patnana, Mohammed Alam

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When acid is pumped into damaged reservoirs for damage removal/stimulation, distorted inflow of acid into the formation occurs caused by acid preferentially traveling into highly permeable regions over low permeable regions, or (in general) into the path of least resistance. This can lead to poor zonal coverage and hence warrants diversion to carry out an effective placement of acid. Diversion is desirably a reversible technique of temporarily reducing the permeability of high perm zones, thereby forcing the acid into lower perm zones. The uniqueness of each reservoir can pose several challenges to engineers attempting to devise optimum and effective diversion strategies. Diversion techniques include mechanical placement and/or chemical diversion of treatment fluids, further sub-classified into ball sealers, bridge plugs, packers, particulate diverters, viscous gels, crosslinked gels, relative permeability modifiers (RPMs), foams, and/or the use of placement techniques, such as coiled tubing (CT) and the maximum pressure difference and injection rate (MAPDIR) methodology. It is not always realized that the effectiveness of diverters greatly depends on reservoir properties, such as formation type, temperature, reservoir permeability, heterogeneity, and physical well characteristics (e.g., completion type, well deviation, length of treatment interval, multiple intervals, etc.). This paper reviews the mechanisms by which each variety of diverter functions and discusses the effect of various reservoir properties on the efficiency of diversion techniques. Guidelines are recommended to help enhance productivity from zones of interest by choosing the best methods of diversion while pumping an optimized amount of treatment fluid. The success of an overall acid treatment often depends on the effectiveness of the diverting agents.

Keywords: diversion, reservoir, zonal coverage, carbonate, sandstone

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11870 Mixed Treatment (Physical-Chemical and Biological) of Ouled Fayet Landfill Leachates

Authors: O. Balamane-Zizi, L. M. Rouidi, A. Boukhrissa, N. Daas, H. Ait-amar

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The objective of this study was to test the possibility of a mixed treatment (physical-chemical and biological) of Ouled Fayet leachates which date of 10 years and has a large fraction of hard COD that can be reduced by coagulation-flocculation. Previous batch tests showed the possibility of applying the physical-chemical and biological treatments separately; the removal efficiencies obtained in this case were not interesting. We propose, therefore, to test the possibility of a combined treatment, in order to improve the quality of the leachates. Estimation of the treatment’s effectiveness was done by analysis of some pollution parameters such as COD, suspended solids, and heavy metals (particularly iron and nickel). The main results obtained after the combination of treatments, show reduction rate of about 63% for COD, 73% for suspended solids and 80% for iron and nickel. We also noted an improvement in the turbidity of treated leachates.

Keywords: landfill leachates, COD, physical-chemical treatment, biological treatment

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11869 Effect of Solution Heat Treatment on Intergranular Corrosion Resistance of Welded Stainless Steel AISI 321

Authors: Amir Mahmoudi

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In this investigation, AISI321 steel after welding by Shilded Metal Arc Welding (SMAW) was solution heat treated in various temperatures and times, and then was sensitizied. Results indicated, increasing of temperature in solution heat treatment raises the sensitization and creates the cavity structure in grain boundaries. Besides, in order to examine the effect of time on solution heat treatment, all samples were solution heat treated at different times and fixed temperature (1050°C). By increasing the time, more chrome carbides were created due to dissolution of delta ferrite phase and reproduce titanium carbides. Additionally, the best process for solution heat treatment for this steel was suggested.

Keywords: stainless steel, solution heat treatment, intergranular corrosion, DLEPR

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11868 Imaging Spectrum of Central Nervous System Tuberculosis on Magnetic Resonance Imaging: Correlation with Clinical and Microbiological Results

Authors: Vasundhara Arora, Anupam Jhobta, Suresh Thakur, Sanjiv Sharma

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Aims and Objectives: Intracranial tuberculosis (TB) is one of the most devastating manifestations of TB and a challenging public health issue of considerable importance and magnitude world over. This study elaborates on the imaging spectrum of neurotuberculosis on magnetic resonance imaging (MRI) in 29 clinically suspected cases from a tertiary care hospital. Materials and Methods: The prospective hospital based evaluation of MR imaging features of neuro-tuberculosis in 29 clinically suspected cases was carried out in Department of Radio-diagnosis, Indira Gandhi Medical Hospital from July 2017 to August 2018. MR Images were obtained on a 1.5 T Magnetom Avanto machine and were analyzed to identify any abnormal meningeal enhancement or parenchymal lesions. Microbiological and Biochemical CSF analysis was performed in radio-logically suspected cases and the results were compared with the imaging data. Clinical follow up of the patients started on anti-tuberculous treatment was done to evaluate the response to treatment and clinical outcome. Results: Age range of patients in the study was between 1 year to 73 years. The mean age of presentation was 11.5 years. No significant difference in the distribution of cerebral tuberculosis was noted among the two genders. Imaging findings of neuro-tuberculosis obtained were varied and non specific ranging from lepto-meningeal enhancement, cerebritis to space occupying lesions such as tuberculomas and tubercular abscesses. Complications presenting as hydrocephalus (n= 7) and infarcts (n=9) was noted in few of these patients. 29 patients showed radiological suspicion of CNS tuberculosis with meningitis alone observed in 11 cases, tuberculomas alone were observed in 4 cases, meningitis with parenchymal tuberculomas in 11 cases. Tubercular abscess and cerebritis were observed in one case each. Tuberculous arachnoiditis was noted in one patient. Gene expert positivity was obtained in 11 out of 29 radiologically suspected patients; none of the patients showed culture positivity. Meningeal form of the disease alone showed higher positivity rate of gene Xpert (n=5) followed by combination of meningeal and parenchymal forms of disease (n=4). The parenchymal manifestation of disease alone showed least positivity rates (n= 3) with gene xpert testing. All 29 patients were started on anti tubercular treatment based on radiological suspicion of the disease with clinical improvement observed in 27 treated patients. Conclusions: In our study, higher incidence of neuro- tuberculosis was noted in paediatric population with predominance of the meningeal form of the disease. Gene Xpert positivity obtained was low due to paucibacillary nature of cerebrospinal fluid (CSF) with even lower positivity of CSF samples in parenchymal form of the manifestation. MRI showed high accuracy in detecting CNS lesions in neuro-tuberculosis. Hence, it can be concluded that MRI plays a crucial role in the diagnosis because of its inherent sensitivity and specificity and is an indispensible imaging modality. It caters to the need of early diagnosis owing to poor sensitivity of microbiological tests more so in the parenchymal manifestation of the disease.

Keywords: neurotuberculosis, tubercular abscess, tuberculoma, tuberculous meningitis

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11867 Housing Delivery in Nigeria’s Urban Areas: The Plight of the Poor in Owerri, Capital of Imo State, Nigeria

Authors: Joachim Onyike

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The Federal Government of Nigeria in 2012 came up with a new National Housing Policy; one of its major objectives was to make housing affordable to the poor. Six years down the line, this study was carried out to find out whether the poor have fared better under the new housing policy. Owerri, the capital of Imo State, was adopted as a case study to mirror the situation nationwide. The study population was made up of low-income civil servants, i.e., grade levels 1–6 in the Imo State Civil Service. The study looked at household size, household income, rental levels, house prices, costs of major building materials, land values, land tenure, the interest rate on mortgages, inflation rate, and the status of government interventions, owing to their obvious effect on housing affordability by the low-income earners. The study made use of physical observations, questionnaires, and interviews as well as library studies to elicit relevant information. Housing affordability by the subject population did not improve. It rather dropped. The study came to the conclusion that in spite of the new National Housing Policy, housing affordability by the low-income earners has not improved. The policy as it affects the poor has not been duly implemented by both Federal and State Governments.

Keywords: house prices, housing affordability, housing policy, land values, low-income earners

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11866 NS5ABP37 Inhibits Liver Cancer by Impeding Lipogenesis and Cholesterogenesis

Authors: Shenghu Feng, Jun Cheng

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The molecular mechanism underlying nonalcoholic fatty liver disease (NAFLD) progression to hepatocellular carcinoma (HCC) remains unknown. In this study, immunohistochemistry staining result showed that NS5ABP37 protein expression decreased as with increasing degree of HCC malignancy. In agreement, NS5ABP37 protein overexpression significantly suppressed cell proliferation, caused G1/S cell cycle arrest, and induced apoptosis by increasing caspase-3/7 activity and cleaved caspase-3 levels. In addition, NS5ABP37 overexpression resulted in decreased intracellular TG and TC contents, with level reduction in SREBPs and downstream effectors. Furthermore, NS5ABP37 overexpression decreased SREBP1c and SREBP2 levels by inducing their respective promoters. Finally, ROS levels and ER-stress were both induced by NS5ABP37 overexpression. These findings together demonstrate that NS5ABP37 inhibits cancer cell proliferation and promotes apoptosis, by altering SREBP-dependent lipogenesis and cholesterogenesis in HepG2 cells and inducing oxidative stress and ER stress.

Keywords: NS5ABP37, liver cancer, lipid metabolism, oxidative stress, ER stress

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11865 Improving Engagement: Dental Veneers, a Qualitative Analysis of Posts on Instagram

Authors: Matthew Sedgwick

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Introduction: Social media continues to grow in popularity and Instagram is one of the largest platforms available. It provides an invaluable method of communication between health care professionals and patients. Both patients and dentists can benefit from seeing clinical cases posted by other members of the profession. It can prompt discussion about how the outcome was achieved and showcases what is possible with the right techniques and planning. This study aimed to identify what people were posting about the topic ‘veneers’ and inform health care professionals as to what content had the most engagement and make recommendations as to how to improve the quality of social media posts. Design: 150 consecutive posts for the search term ‘veneers’ were analyzed retrospectively between 21st October 2021 to 31st October 2021. Non-English language posts duplicated posts, and posts not about dental veneers were excluded. After exclusions were applied, 80 posts were included in the study for analysis. The content of the posts was analyzed and coded and the main themes were identified. The number of comments, likes and views were also recorded for each post. Results: The themes were: before and after treatment, cost, dental training courses, treatment process and trial smiles. Dentists were the most common posters of content (82.5%) and it was interesting to note that there were no patients who posted about treatment in this sample. The main type of media was photographs (93.75%) compared to video (6.25%). Videos had an average of 45,541 views and more comments and likes than the average for photographs. The average number of comments and likes per post were 20.88 and 761.58, respectively. Conclusion: Before and after photographs were the most common finding as this is how dentists showcase their work. The study showed that videos showing the treatment process had more engagement than photographs. Dentists should consider making video posts showing the patient journey, including before and after veneer treatment, as this can result in more potential patients and colleagues viewing the content. Video content could help dentists distinguish their posts from others as it can also be used across other platforms such as TikTok or Facebook reaching a wider audience. More informative posts about how the result has shown are achieved required, including potential costs. This will help increase transparency regarding this treatment method, including the financial and potential biological cost to teeth. As a result, this will improve patient understanding and become an invaluable adjunct in informed consent.

Keywords: content analysis, dental veneers, Instagram, social media

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11864 Photobleaching Kinetics and Epithelial Distribution of Hexylaminoleuilinate Induced PpIX in Rat Bladder Cancer

Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

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Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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