Search results for: non-small-cell lung carcinoma

Authors: Mohammad Ranjbar, Mohammad Bazyar, Blake Angell, Thomas Lung, Yibeltal Assefa

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Background: Current health insurance programs in Iran suffer from low enrolment and are not sufficient to attain the country to universal health coverage (UHC). We hypothesize that improving the enrollment rate and moving towards a more sustainable UHC can be achieved by improving the benefits package and providing new incentives. The objective of this study is to assess public preferences and willingness to pay (WTP) for social health insurance (SHI) in Iran. Methods: A discrete choice experiment (DCE) was conducted in 2021, using a self-administered questionnaire on 500 participants to estimate WTP and determine individual preferences for the SHI in Yazd, Iran. Respondents were presented with an eight-choice set and asked to select their preferred one. In each choice set, scenarios were described by eight attributes with varying levels. The conditional logit regression model was used to analyze the participants' preferences. Willingness to pay for each attribute was also calculated. Results: Most included attributes were significant predictors of the choice of a health insurance package. The maximum coverage of hospitalization costs in the private sector, ancillary services such as glasses, canes, etc., as well as coverage for hospitalization costs in the public sector and drug costs, were the most important determining factors for this choice. Coverage of preventive dental care did not significantly influence respondent choices. Estimating WTP showed that individuals are willing to pay more for higher financial protection, particularly against private sector costs; the WTP to increase the coverage of hospitalization costs in the private sector from 50% to 90% is estimated at 362,068 IR, Rials per month. Conclusion: This study identifies the key factors that the population value with regard to health insurance and the tradeoffs they are willing to make between them. Hospitalization, drugs, and ancillary services were the most important determining factors for their choice. The data suggest that additional resources coming into the Iranian health system might best be prioritized to cover hospitalization and drug costs and those associated with ancillary services.

Keywords: social health insurance, preferences, discrete choice experiment, willingness to pay

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Authors: Tarek K. Jalouta, Jolietta R. Holliman, Kathryn R. Burke, Kathleen M. Bewley-Thomas

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Background: Chronic hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma. In the United States, HCV screening awareness, treatment, and linkage to care are under continues ascending progress. However, still millions of people are asymptomatically infected and undiagnosed yet. Through this community mission, we sought to identify the best and the newest strategies to identify those infected people to educate them, link them to care and cure them. Methods: We have identified patients that did not have a prior HCV screening in our Electronic medical record (EMR) including all our different hospital locations (South Suburban Chicago, Northern, Western and Central Indiana). Providing education to all Primary care/Gastroenterology/Infectious diseases providers and staff in the clinic to increase awareness of the HCV screening. Health-related quality of life, chronic clinical complications, and demographics data were collected for each patient. All outcomes of HCV antibody-reactive and HCV RNA–positive results were identified and statistically analyzed. Results: From July 2016 to July 2018 we screened 35,720 individuals of birth cohort in our different Franciscan’s health medical centers. Of the screened population, 986 (2.7%) individuals were HCV AB-reactive. Of those, 319 (1%) patients were HCV RNA-positive, and 264 patients were counseled and linked to providers. 34 patients initiated anti-HCV therapy with successful treatment. Conclusions: Our HCV screening augmentation project considered the largest screening program in the Midwest. Augmenting the HCV screening process through creating a Best Practice Alert (BPA) in the EMR (Epic Sys.) and point of care testing could be helpful. Although continued work is required, our team is working on increase screening through adding HCV test to CBC-Panels in Emergency Department settings, phone calls to all birth cohort individuals through Robo-Calling System aimed to reach 75,000 individuals by 2019. However, a better linkage to care and referral monitoring system to all HCV RNA positive patients is still needed, and access to therapy, especially for uninsured patients, is challenging.

Keywords: chronic hepatitis C, chronic hepatitis C treatment, chronic hepatitis C screening, chronic hepatitis C prevention, liver cancer

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Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

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Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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Authors: Iva Blazkova, Amitava Moulick, Vedran Milosavljevic, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Doxorubicin is one of the most commonly used and the most effective chemotherapeutic drugs. This antracycline drug isolated from the bacteria Streptomyces peuceticus var. caesius is sold under the trade name Adriamycin (hydroxydaunomycin, hydroxydaunorubicin). Doxorubicin is used in single therapy to treat hematological malignancies (blood cancers, leukaemia, lymphoma), many types of carcinoma (solid tumors) and soft tissue sarcomas. It has many serious side effects like nausea and vomiting, hair lost, myelosupression, oral mucositis, skin reactions and redness, but the most serious one is the cardiotoxicity. Because of the risk of heart attack and congestive heart failure, the total dose administered to patients has to be accurately monitored. With the aim to lower the side effects and to targeted delivery of doxorubicin into the tumor tissue, the different nanoparticles are studied. The drug can be bound on a surface of nanoparticle, encapsulated in the inner cavity, or incorporated into the structure of nanoparticle. Among others, carbon nanoparticles (graphene, carbon nanotubes, fullerenes) are highly studied. Besides the number of inorganic nanoparticles, a great potential exhibit also organic ones mainly lipid-based and polymeric nanoparticle. The aim of this work was to perform a toxicity study of free doxorubicin compared to doxorubicin conjugated with various nanotransporters. The effect of liposomes, fullerenes, graphene, and carbon nanotubes on the toxicity was analyzed. As a first step, the binding efficacy of between doxorubicin and the nanotransporter was determined. The highest efficacy was detected in case of liposomes (85% of applied drug was encapsulated) followed by graphene, carbon nanotubes and fullerenes. For the toxicological studies, the chicken embryos incubated under controlled conditions (37.5 °C, 45% rH, rotation every 2 hours) were used. In 7th developmental day of chicken embryos doxorubicin or doxorubicin-nanotransporter complex was applied on the chorioallantoic membrane of the eggs and the viability was analyzed every day till the 17th developmental day. Then the embryos were extracted from the shell and the distribution of doxorubicin in the body was analyzed by measurement of organs extracts using laser induce fluorescence detection. The chicken embryo mortality caused by free doxorubicin (30%) was significantly lowered by using the conjugation with nanomaterials. The highest accumulation of doxorubicin and doxorubicin nanotransporter complexes was observed in the liver tissue

Keywords: doxorubicin, chicken embryos, nanotransporters, toxicity

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Authors: A. A. Md. Ryhan Uddin, Swarup Das, Rajesh Barua, Joheb Hasan, Rashedul Islam

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Background: The herbicide has toxicological importance because some of them are associated with high mortality rates due to respiratory failure. Organophosphate poisoning (OPC) & Paraquat self-poisoning is a major clinical and public health problems in low and middle-income countries across much of South Asia. Paraquat was not used as a common suicidal agent previously in Bangladesh. We report a case of 15 years old female admitted to the ER with a history of nausea & vomiting after ingestion of an unknown substance in a suicidal attempt, later identified as mixed poisoning- OPC & Paraquat. She was initially asymptomatic but later developed renal shutdown & lung injuries as well as pneumothorax, referred to as Daisley Barton Syndrome. Objective: This case report aims to alert spontaneous pneumothorax in mixed poisoning on uncommon forms of presentation. Pneumothorax in a patient with paraquat poisoning is a less unusual but underdiagnosed finding. It has a high index of early mortality. Case history: The patient's attendant complained about nausea followed by vomiting, which was nonprojectile & contains undigested food materials first, then gastric juice later. After a few hours, she also complains of urinary retention. Her family members treated her with some home remedies for her initial symptoms, but all attempts failed. After admission, the patient was initially asymptomatic. Through repeated history taking, her attendant showed a bottle of OPC in liquid form, which they suspected that she may have ingested some of the liquid from that bottle accidentally or attempted Suicide. So, management started for OPC poisoning. She responded well initially, but on 4th day of admission, the patient's condition became deteriorating. After the workout with the family member, 2nd bottle of Pesticide was discovered, which was Paraquat. Conclusion: Physicians should be aware of the symptoms of mixed poisoning and the timely use of urine dithionate testing for early detection and treatment. Pneumothorax is an early predictor of mortality in patients with paraquat poisoning.

Keywords: pneumothorax, suicide, dithionate, OPC, herbicide

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Authors: Frederick Anlimah, Vinod Gopaldasani, Catherine MacPhail, Brian Davies

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Aim: This study aims to identify the barriers and challenges hindering the implementation of effective controls and the adoption of safe work practices to protect workers from respirable crystalline silica (RCS) exposure. Problem or Situation: Tunnelling is one of many occupations that expose workers to the harmful effects of respirable crystalline silica. Despite various control measures, such as engineering controls and personal protective equipment, exposures remain inadequately controlled, leading to incurable silicosis and other severe illnesses, such as lung cancer. Methods: The research involved surveying tunnel construction workers, conducting interviews, and facilitating focus group discussions. Additionally, site observations and content analysis of work procedures and instructions were performed. Results: Preliminary data analysis reveals notable findings. While there is a commendable level of knowledge and commitment among management and workers concerning RCS exposure in tunnelling, there is a striking lack of prioritization regarding dust control. Moreover, the risks associated with dust exposure are not sufficiently acknowledged. Additionally, the data suggests that engineers and supervisors responsible for implementing dust controls often possess limited knowledge regarding the factors influencing the effectiveness of these measures. These findings emphasise the need for a paradigm shift, including higher prioritisation of dust control, adoption of holistic dust reduction strategies, and enhanced knowledge about effective control measures. Conclusion: This research shed light on tunnel construction workers' barriers and challenges in protecting themselves from RCS exposure. This knowledge will be essential in developing interventions and strategies to enhance dust exposure and prevent the adverse health effects of respirable crystalline silica exposure in tunnelling and similar industries.

Keywords: respirable crystalline silica, dust control, worker practices, exposure prevention, silicosis

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Authors: Loubna Khalile, Hicham Lahlaoi, Hassan Rhinane, A. Kaoukaya, S. Fal

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Green spaces is an essential element, they contribute to improving the quality of lives of the towns around them. They are a place of relaxation, walk and rest a playground for sport and youths. According to United Nations Organization Forests cover 31% of the land. In Morocco in 2013 that cover 12.65 % of the total land area, still, a small proportion compared to the natural needs of forests as a green lung of our planet. The Benslimane Forest is a large green area It belongs to Chaouia-Ouardigha Region and Greater Casablanca Region, it is located geographically between Casablanca is considered the economic and business Capital of Morocco and Rabat the national political capital, with an area of 12261.80 Hectares. The essential problem usually encountered in suburban forests, is visitation and tourism pressure it is anthropogenic actions, as well as other ecological and environmental factors. In recent decades, Morocco has experienced a drought year that has influenced the forest with increasing human pressure and every day it suffers heavy losses, as well as over-exploitation. The Moroccan forest ecosystems are weak with intense ecological variation, domanial and imposed usage rights granted to the population; forests are experiencing a significant deterioration due to forgetfulness and immoderate use of forest resources which can influence the destruction of animal habitats, vegetation, water cycle and climate. The purpose of this study is to make a model of the degree of degradation of the forest and know the causes for prevention by using remote sensing and geographic information systems by introducing climate and ancillary data. Analytic hierarchy process was used to find out the degree of influence and the weight of each parameter, in this case, it is found that anthropogenic activities have a fairly significant impact has thus influenced the climate.

Keywords: analytic hierarchy process, degradation, forest, geographic information system

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Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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Authors: Manisha Bal, Remya Chinnamma Jose, B.C. Meikap

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Dust particles suspended in air are a major source of air pollution. A self-priming submerged venturi scrubber proven very effective in cases of handling nuclear power plant accidents is an efficient device to remove dust particles from the air and thus aids in pollution control. Venturi scrubbers are compact, have a simple mode of operation, no moving parts, easy to install and maintain when compared to other pollution control devices and can handle high temperatures and corrosive and flammable gases and dust particles. In the present paper, fly ash particles recognized as a high air pollutant substance emitted mostly from thermal power plants is considered as the dust particle. Its exposure through skin contact, inhalation and indigestion can lead to health risks and in severe cases can even root to lung cancer. The main focus of this study is on the removal of fly ash particles from polluted air using a self-priming venturi scrubber in submerged conditions using water as the scrubbing liquid. The venturi scrubber comprising of three sections: converging section, throat and diverging section is submerged inside a water tank. The liquid enters the throat due to the pressure difference composed of the hydrostatic pressure of the liquid and static pressure of the gas. The high velocity dust particles atomize the liquid droplets at the throat and this interaction leads to its absorption into water and thus removal of fly ash from the air. Detailed investigation on the scrubbing of fly ash has been done in this literature. Experiments were conducted at different throat gas velocities, water levels and fly ash inlet concentrations to study the fly ash removal efficiency. From the experimental results, the highest fly ash removal efficiency of 99.78% is achieved at the throat gas velocity of 58 m/s, water level of height 0.77m with fly ash inlet concentration of 0.3 x10⁻³ kg/Nm³ in the submerged condition. The effect of throat gas velocity, water level and fly ash inlet concentration on the removal efficiency has also been evaluated. Furthermore, experimental results of removal efficiency are validated with the developed empirical model.

Keywords: dust particles, fly ash, pollution control, self-priming venturi scrubber

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Authors: Chikwelu Edward Emenike, Ogbuagu Uchenna Fredrick

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About 34% of the solar radiant energy reaching the earth is immediately reflected back to space as incoming radiation by clouds, chemicals, dust in the atmosphere and by the earth’s surface. Most of the remaining 66% warms the atmosphere and land. Most of the incoming solar radiation not reflect away is degraded into low-quality heat and flows into space. The rate at which this energy returns to space as low-quality heat is affected by the presence of molecules of greenhouse gases. Gaseous emission was measured with the aid of Growen gas Analyzer with a digital readout. Total measurements of eight parameters of twelve selected sample locations taken at two different seasons within two months were made. The ambient air quality investigation in Anambra State has shown the overall mean concentrations of gaseous emission at twelve (12) locations. The mean gaseous emissions showed (NO2=0.66ppm, SO2=0.30ppm, CO=43.93ppm, H2S=2.17ppm, CH4=1.27ppm, CFC=1.59ppb, CO2=316.33ppm, N2O=302.67ppb and O3=0.37ppm). These values do not conform to the National Ambient Air Quality Standard (NAAQS) and thus contribute significantly to the global warming. Because some of these gaseous emissions (SO2, NO2) are oxidizing agents, they act as irritants that damage delicate tissues in the eyes and respiratory passages. These can impair lung function and trigger cardiovascular problems as the heart tries to compensate for lack of Oxygen by pumping faster and harder. The major sources of air pollution are transportation, industrial processes, stationary fuel combustion and solid waste disposal, thus much is yet to be done in a developing country like Nigeria. Air pollution control using pollution-control equipment to reduce the major conventional pollutants, relocating people who live very close to dumpsites, processing and treatment of gases to produce electricity, heat, fuel and various chemical components should be encouraged.

Keywords: ambient air, atmosphere, greenhouse gases, anambra state

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Authors: Aarti Agarwal, Ajmal Khan

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Background and Objective: Breathing difficulty is most distressing symptom for the patient and their caregivers providing palliative care to individuals with advanced malignancy. It needs to be tackled effectively and sometimes preemptively to provide relief from respiratory obstruction. Interventional procedures like tracheal stenting are becoming increasingly popular as a part of palliation for respiratory symptoms. We present a case of esophageal tumor earlier stented by Gastroenterologist to maintain esophageal patency, but the tumor outgrew to produce tracheal infiltration and thereby causing airway obstruction. Method and Result: 62-year-old man presented with unresectable Carcinoma oesophagus with inability to swallow. A metallic stent was placed by the gastroenterologist, to maintain esophageal patency and enable patient to swallow. Two months later, the patient returned to hospital in emergency with respiratory distress. CT neck and thorax revealed tumor infiltration through posterior tracheal wall. Lower extent of the tumor was till 1 cm above the carina. Airway stenting with Tracheo bronchial stent with Y configuration was planned under general anaesthesia with airway blocks. Superior Laryngeal Nerve Block, Glossopharyngeal block and Trans tracheal infiltration of local anaesthetics were performed. The patient was sedated with Fentanyl, Midazolam and propofol infusion but was breathing spontaneously. Once the rigid bronchoscope was placed inside trachea, breathing was supported with oxygen and sevoflurane. Initially, the trachea was cleared of tumor by coring. After creating space, tracheal stent was positioned and deployed. After stent placement patient was awakened, suctioned and nebulized. His respiratory stridor relieved instantaneously and was shifted to recovery. Conclusion: Airway blocks help in decreasing the incidence and severity of coughing during airway instrumentation thereby help in proper stent placement. They also reduce the requirement of general anaesthetics and hasten the post stenting recovery. Airway stent provided immediate relief to patient from symptoms of respiratory difficulty. Decision for early tracheal stenting may be taken for a select group of patients with high propensity for local spread, thereby avoiding respiratory complications and providing better quality of life in patients with inoperable malignancy.

Keywords: tracheal stent, respiratory difficulty, esophageal tumor, anaesthetic management

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Authors: Sardar Khana, Zar Ali Khana

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Rapid industrial development and urbanization contribute a lot to wastewater discharge. The wastewater enters into natural aquatic ecosystems from industrial activities and considers as one of the main sources of water pollution. Discharge of effluents loaded with heavy metals into the surrounding environment has become a key issue regarding human health risk, environment, and food chain contamination. Nickel causes fatigue, cancer, headache, heart problems, skin diseases (Nickel Itch), and respiratory disorders. Nickel compounds such as Nickel Sulfide and Nickel oxides in industrial environment, if inhaled, have an association with an increased risk of lung cancer. Therefore the removal of Nickel from effluents before discharge is necessary. Removal of Nickel by low-cost biosorbents is an efficient method. This study was aimed to investigate the efficiency of activated carbon and Pinusroxburgiisaw dust for the removal of Nickel from industrial effluents using commercial Activated Carbon, and raw P.roxburgii saw dust. Batch and column adsorption experiments were conducted for the removal of Nickel. The study conducted indicates that removal of Nickel greatly dependent on pH, contact time, Nickel concentration, and adsorbent dose. Maximum removal occurred at pH 9, contact time of 600 min, and adsorbent dose of 1 g/100 mL. The highest removal was 99.62% and 92.39% (pH based), 99.76% and 99.9% (dose based), 99.80% and 100% (agitation time), 92% and 72.40% (Ni Conc. based) for P.roxburgii saw dust and activated Carbon, respectively. Similarly, the Ni removal in column adsorption was 99.77% and 99.99% (bed height based), 99.80% and 99.99% (Concentration based), 99.98%, and 99.81% (flow rate based) during column studies for Nickel using P.Roxburgiisaw dust and activated carbon, respectively. Results were compared with Freundlich isotherm model, which showed “r2” values of 0.9424 (Activated carbon) and 0.979 (P.RoxburgiiSaw Dust). While Langmuir isotherm model values were 0.9285 (Activated carbon) and 0.9999 (P.RoxburgiiSaw Dust), the experimental results were fitted to both the models. But the results were in close agreement with Langmuir isotherm model.

Keywords: nickel removal, batch, and column, activated carbon, saw dust, plant uptake

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

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

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

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Authors: Nicholas Bayfield, Liam Bibo, Kaushelandra Rathore, Lucas Sanders, Mark Newman

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INTRODUCTION: Surgical pulmonary embolectomy is an established therapy for acute pulmonary embolism causing right heart dysfunction and haemodynamic instability. Massive intraoperative airway haemorrhage is a rare complication of pulmonary embolectomy. We present our institutional experience with massive airway haemorrhage complicating pulmonary embolectomy and discuss optimal therapeutic strategies. METHODS: A retrospective review of emergent surgical pulmonary embolectomy patients was undertaken. Cases complicated by massive intra-operative airway haemorrhage were identified. Intra- and peri-operative management strategies were analysed and discussed. RESULTS: Of 76 patients undergoing emergent or salvage pulmonary embolectomy, three cases (3.9%) of massive intraoperative airway haemorrhage were identified. Haemorrhage always began on weaning from cardiopulmonary bypass. Successful management strategies involved intraoperative isolation of the side of bleeding, occluding the affected airway with an endobronchial blocker, institution of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) and reversal of anticoagulation. Running the ECMO without heparinisation allows coagulation to occur. Airway haemorrhage was controlled within 24 hours of operation in all patients, allowing re-institution of dual lung ventilation and decannulation from ECMO. One case in which positive end-expiratory airway pressure was trialled initially was complicated by air embolism. Although airway haemorrhage was controlled successfully in all cases, all patients died in-hospital for reasons unrelated to the airway haemorrhage. CONCLUSION: Massive intraoperative airway haemorrhage during pulmonary embolectomy is a rare complication with potentially catastrophic outcomes. Re-perfusion alveolar and capillary injury is the likely aetiology. With a systematic approach to management, airway haemorrhage can be well controlled intra-operatively and often resolves within 24 hours. Stopping blood flow to the pulmonary arteries and support of oxygenation by the institution of VA ECMO is important. This management has been successful in our 3 cases.

Keywords: pulmonary embolectomy, cardiopulmonary bypass, cardiac surgery, pulmonary embolism

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Authors: Ching-Yuan Chen, Lung-Kwang Pan

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Objective: Back pain is a major health problem costing billions of health budgets annually in Taiwan. Thousands of back pain surgeries are performed annually with up to 40% of patients complaining of back pain at time of post-surgery causing failed back surgery syndrome (FBSS), although diagnosis in these patients may be complex. The aim of study is to assess the feasibility of using bone SPECT-CT imaging to localize the active lesions causing persistent, recurrent or new backache after spine surgery. Materials and Methods: Bone SPECT-CT imaging was performed after the intravenous injection of 20 mCi of 99mTc-MDP for all the patients with diagnosis of FBSS. Patients were evaluated using status of subjectively pain relief, functional improvement and degree of satisfaction by reviewing the medical records and questionnaires in a 2 more years’ follow-up. Results: We enrolled a total of 16 patients were surveyed in our hospital from Jan. 2015 to Dec. 2016. Four people on SPEC/CT imaging ensured significant lesions were undergone a revised surgery (surgical treatment group). The mean visual analogue scale (VAS) decreased 5.3 points and mean Oswestry disability index (ODI) improved 38 points in the surgical group. The remaining 12 on SPECT/CT imaging were diagnosed as no significant lesions then received drug treatment (medical treatment group). The mean VAS only decreased 2 .1 point and mean ODI improved 12.6 points in the medical treatment group. In the posttherapeutic evaluation, the pain of the surgical treatment group showed a satisfactory improvement. In the medical treatment group, 10 of the 12 were also satisfied with the symptom relief while the other 2 did not improve significantly. Conclusions: Findings on SPECT-CT imaging appears to be easily explained the patients' pain. We recommended that SPECT/CT imaging was a feasible and useful clinical tool to improve diagnostic confidence or specificity when evaluating patients with FBSS.

Keywords: failed back surgery syndrome, oswestry disability index, SPECT-CT imaging, 99mTc-MDP, visual analogue scale

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Authors: Fergal Fouhy, Alan O’Keeffe, Sean Costelloe, Michael Clarkson

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Background: Sarcoidosis is a systemic, non-infectious disease of unknown aetiology, characterized by non-caseating granulomatous inflammation. The lung is most often affected (90%); however, the condition can affect all organs, including the kidneys. There is limited evidence describing the incidence and characteristics of renal involvement in sarcoidosis. Serum angiotensin-converting enzyme (ACE) is a recognised biomarker used in the diagnosis and monitoring of sarcoidosis. Methods: A single-centre, retrospective cohort study of patients presenting to Cork University Hospital (CUH) in 2015 with first-time elevations of serum ACE was performed. This included an initial database review of ACE and other biochemistry results, followed by a medical chart review to confirm the presence or absence of sarcoidosis and management thereof. Acute kidney injury (AKI) was staged using the AKIN criteria, and chronic kidney disease (CKD) was staged using the KDIGO criteria. Follow-up was assessed over five years tracking serum creatinine, serum calcium, and estimated glomerular filtration rates (eGFR). Results: 119 patients were identified as having a first raised serum ACE in 2015. Seventy-nine male patients and forty female patients were identified. The mean age of patients identified was 47 years old. 11% had CKD at baseline. 18% developed an AKI at least once within the next five years. A further 6% developed CKD during this time period. 13% developed hypercalcemia. The patients within the lowest quartile of serums ACE had an incidence of sarcoidosis of 5%. None of this group developed hypercalcemia, 23% developed AKI, and 7% developed CKD. Of the patients with a serum ACE in the highest quartile, almost all had documented diagnoses of sarcoidosis with an incidence of 96%. 3% of this group developed hypercalcemia, 13% AKI and 3% developed CKD. Conclusions: There was an unexpectedly high incidence of AKI in patients who had a raised serum ACE. Not all patients with a raised serum ACE had a confirmed diagnosis of sarcoidosis. There does not appear to be a relationship between increased serum ACE levels and increased incidence of hypercalcaemia, AKI, and CKD. Ideally, all patients should have biopsy-proven sarcoidosis. This is an initial study that should be replicated with larger numbers and including multiple centres.

Keywords: sarcoidosis, acute kidney injury, chronic kidney disease, hypercalcemia

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Authors: Andres Gonzalez, Adam Boies, Jacob Swanson, David Kittelson

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The concern of the indoor air quality (IAQ) has been increasing due to its risk to human health. The smoking, sweeping, and stove and stovetop use are the activities that have a major contribution to the indoor air pollution. Outdoor air pollution also affects IAQ. The most important factors over IAQ from cooking activities are the materials, fuels, foods, and ventilation. The low-cost, mobile air quality monitoring (LCMAQM) sensors, is reachable technology to assess the IAQ. This is because of the lower cost of LCMAQM compared to conventional instruments. The IAQ was assessed, using LCMAQM, during cooking activities in a University of Minnesota graduate-housing evaluating different ventilation systems. The gases measured are carbon monoxide (CO) and carbon dioxide (CO₂). The particles measured are particle matter (PM) _2.5 micrometer (µm) and lung deposited surface area (LDSA). The measurements are being conducted during April 2019 in Como Student Community Cooperative (CSCC) that is a graduate housing at the University of Minnesota. The measurements are conducted using an electric stove for cooking. The amount and type of food and oil using for cooking are the same for each measurement. There are six measurements: two experiments measure air quality without any ventilation, two using an extractor as mechanical ventilation, and two using the extractor and windows open as mechanical and natural ventilation. 3The results of experiments show that natural ventilation is most efficient system to control particles and CO₂. The natural ventilation reduces the concentration in 79% for LDSA and 55% for PM_2.5, compared to the no ventilation. In the same way, CO₂ reduces its concentration in 35%. A well-mixed vessel model was implemented to assess particle the formation and decay rates. Removal rates by the extractor were significantly higher for LDSA, which is dominated by smaller particles, than for PM_2.5, but in both cases much lower compared to the natural ventilation. There was significant day to day variation in particle concentrations under nominally identical conditions. This may be related to the fat content of the food. Further research is needed to assess the impact of the fat in food on particle generations.

Keywords: cooking, indoor air quality, low-cost sensor, ventilation

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

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

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

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Authors: Hee-Young Song

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Background and objectives: In 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations proposed a multidimensional assessment of patients’ conditions that included both functional parameters and patient-reported outcomes, with the aim to provide a comprehensive assessment of the disease, thus meeting both the needs of the patient and the role of the physician. However, few studies have evaluated patient-reported outcomes as well as objective functional assessments among individuals with chronic obstructive pulmonary disease (COPD) in clinical practice in Korea. This study was undertaken to explore the relationship between functional status assessed by the 6-minute walking distance (MWD) test and subjective health status reported by stable patients with COPD residing in community. Methods: A cross-sectional descriptive study was conducted with 118 stable COPD patients aged 69.4 years old and selected by a convenient sampling from an outpatient department of pulmonology in a tertiaryhospitals. The 6-MWD test was conducted according to standardized instructions. Participants also completed a constructed questionnaire including general characteristics, smoking history, dyspnea by modified medical research council (mMRC) scale, and health status by COPD assessment test (CAT). Anthropometric measurements were performed for body mass index (BMI). Medical records were reviewed to obtain disease-related characteristics including duration of the disease and forced expiratory volume in 1 second (FEV1). Data were analyzed using PASW statistics 20.0. Results: Mean FEV1% of participants was 63.51% and mean 6-MWD and CAT scores were 297.54m and 17.7, respectively. The 6-MWD and CAT showed significant negative correlations (r= -.280, p=.002); FEV1 and CAT did as well correlations (r= -.347, p < .001). Conclusions: Findings suggest that the better functional status an individual with COPD has, the better subjective health status is, and provide the support for using patient-reported outcomes along with functional parameters to facilitate comprehensive assessment of COPD patients in real clinical practices.

Keywords: chronic obstructive pulmonary disease, COPD assessment test, functional status, patient-reported outcomes

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Authors: Vanitha Varadharaj, Vijalakshmi Krishnamurthy

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Annona squamosa Linn, commonly known as Sugar apple, belonging to the family Annonaceae, is said to show varied medicinal effects, including insecticide, antiovulatory and abortifacient. The alkaloid and flavonoids present in Annona squamosa leaf has proved to have antioxidant activity. The present work has been planned to investigate the effect of ethanolic leaf extract of Annona squamosa leaf on Den Induced wistar albino rats. The study was carried out to analyze the biochemical Parmeters like Total Proteins, Bilirubin, Enzymatic and Non –Enzymatic enzymes, Marker enzymes and Tumor markers in serum and also the histopathological studies in liver is carried out in control and DEN induced rats. Supplementation of ELAS (Ethanolic Leaf Extract Of Annona squamosa) reduced the liver weight and also reduced the tumour incidence. Chemoprevention group showed near normal values of bilirubin when compared with the control rats. Total protein was decreased in the cancer bearing group and on treatment with the extract the levels of protein were restored. Both in pre and post treatment group, the activities of enzymatic antioxidants such as superoxide dismutase, catalase, and Glutathione peroxidase were increased but in pre treated animals it was more effective than post treated animals. The non- enzymatic antioxidants such as vitamin C and vitamin E were brought back to normal level significantly in post and pre treated animals. Activities of marker enzymes such as SGOT, SGPT, ALP, γ GT were significantly elevated in the serum of cancer animals and the values returned to normal after treatment with the extract suggesting the hepato protective effect of the extract. Lipid peroxide was found to be elevated in the cancer induced group. This condition was brought back to the normal in the pre and post treated animals with ELAS. Histological examination also confirmed the anti- carcinogenic potential of ELAS, Cancer induced groups had a triple fold increase in their AFP values when compared to other groups. DEN treatment increased the level of AFP expression while ELAS partially counteracted the effect of it. So the scientific validation obtained from this study may pave way to many budding scientists to find new drugs from Annona squamosa for various ailments.

Keywords: annona squamosa, biochemical parmeters, cancer, leaf extract

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Authors: Sidra Suleman, Maliha Suleman, Stephen Brindley

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Oral rehabilitation of head and neck cancer patients plays a crucial role in the quality of life for such individuals post-treatment. Placement of dental implants or implant-retained prostheses can help restore oral function and aesthetics, which is often compromised following surgery. Conventional prosthodontic techniques can be insufficient in rehabilitating such patients due to their altered anatomy and reduced oral competence. Hence, there is a strong clinical need for the placement of dental implants. With an increasing incidence of head and neck cancer patients, the demand for such treatment is rising. Aim: The aim of the study was to determine the survival rate of dental implants in head and neck cancer patients placed at the Restorative and Maxillofacial Department, Royal Stoke University Hospital (RSUH), United Kingdom. Methodology: All patients who received dental implants between January 1, 2013 to December 31, 2020 were identified. Patients were excluded based on three criteria: 1) non-head and neck cancer patients, 2) no outpatient follow-up post-implant placement 3) provision of non-dental implants. Scanned paper notes and electronic records were extracted and analyzed. Implant survival was defined as fixtures that had remained in-situ / not required removal. Sample: Overall, 61 individuals were recruited from the 143 patients identified. The mean age was 64.9 years, with a range of 35 – 89 years. The sample included 37 (60.7%) males and 24 (39.3%) females. In total, 211 implants were placed, of which 40 (19.0%) were in the maxilla, 152 (72.0%) in the mandible and 19 (9.0%) in autogenous bone graft sites. Histologically 57 (93.4%) patients had squamous cell carcinoma, with 43 (70.5%) patients having either stage IVA or IVB disease. As part of treatment, 42 (68.9%) patients received radiotherapy, which was carried out post-operatively for 29 (69.0%) cases. Whereas 21 (34.4%) patients underwent chemotherapy, 13 (61.9%) of which were post-operative. The Median follow-up period was 21.9 months with a range from 0.9 – 91.4 months. During the study, 23 (37.7%) patients died and their data was censored beyond the date of death. Results: In total, four patients who had received radiotherapy had one implant failure each. Two mandibular implants failed secondary to osteoradionecrosis, and two maxillary implants did not survive as a result of failure to osseointegrate. The overall implant survival rates were 99.1% at three years and 98.1% at both 5 and 7 years. Conclusions: Although this data shows that implant failure rates are low, it highlights the difficulty in predicting which patients will be affected. Future studies involving larger cohorts are warranted to further analyze factors affecting outcomes.

Keywords: oncology, dental implants, survival, restorative

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Authors: Munkhtuul G., Bolortsetseg Z., Lutzul M., Sugar N., Nyamdorj D., Nomundari B., Zesemdorj O., Erdenebayar N., Lkhagvasuren T. S., Munkhbayarlakh S., Bayasgalan T. Uurtuya S. H.

Abstract:

Background: Elevated serum uric acid (SUA) levels are observed in metabolic and cardiovascular conditions as an early predictor of metabolic syndrome (MS). Hyperuricemia, characterised by high uric acid levels in serum, increases the risk of developing MS by 1.6 times. Being overweight and obese significantly contributes to developing MS and cardiovascular disorders. In Mongolia, the prevalence of overweight and obesity is reaching 48.8% among individuals aged 15 to 49 years, indicating a potential surge in the incidence of MS, cardiovascular disorders, diabetes mellitus, and gout.Objective: This study aimed to determine the SUA levels in men diagnosed with MS and investigate the factors influencing these levels.Methods: A total of 119 men aged 30-60, who underwent preventive examinations and resided in Ulaanbaatar city, were included in the study. The criteria established by the International Diabetes Federation (IDF), American Heart Association (AHA), and the National Heart, Lung, and Blood Institute (NHLBI) were employed to define metabolic syndrome. Hyperuricemia was defined as SUA levels ≥7 mg/dL. Dietary intake was evaluated through the 24-hour recall method.Results: The study revealed that the prevalence of MS among the participants was 42.9% (n=51), with hyperuricemia observed in 16.8% (n=20) of the individuals. Among men diagnosed with MS, 21.3% (n=10) exhibited hyperuricemia. The mean SUA levels were as follows: 4.7±0.8 mg/dL in the healthy group, 5.9±1.1 mg/dL in men without MS but presenting central obesity, and 6.2±1.3 mg/dL in men with MS. After adjusting for age and body mass index (BMI), a positive correlation was observed between SUA levels and triglycerides (β=0.93) as well as lipid accumulation product (LAP) (β=0.92) in men with MS. In the central obesity group, SUA levels exhibited a positive correlation with triglycerides (β=0.91), visceral adiposity index (VAI) (β=0.73), LAP (β=0.92), and cardiometabolic index (CMI) (β=0.69). The risk of hyperuricemia increased by 3.29 times with elevated triglycerides and 3.53 times with an increased LAP.Conclusion: The findings indicate that abdominal fat accumulation, as indicated by elevated triglyceride levels and LAP, is associated with increased SUA levels in men with MS. However, no significant relationship was observed between SUA levels and dietary intake.

Keywords: central obesity, obesity, triglycerides, hyperuricemia

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Authors: Xiaoquan Huang, Congcong Li, Tingting Wei, Changcun Bai, Na Liu, Meng Tang

Abstract:

Silver is often doped on nano-titanium dioxide photocatalysts (Ag-TiO₂) by photodeposition method to improve their utilization of visible-light while increasing the toxicity of TiO₂。 However, it is not known what factors influence this toxicity and how to reduce toxicity while maintaining the maximum catalytic activity. In this study, Ag-TiO₂ photocatalysts were synthesized by the photodeposition method with different silver content (AgC) and photodeposition time (PDT). Characterization and catalytic experiments demonstrated that silver was well assembled on TiO₂ with excellent visible-light catalytic activity, and the size of silver increased with PDT. In vitro, the cell viability of lung epithelial cells A549 and BEAS-2B showed that the higher content and smaller size of silver doping caused higher toxicity. In vivo, Ag-TiO₂ catalysts with lower AgC or larger silver particle size obviously caused less pulmonary pro-inflammatory and pro-fibrosis responses. However, the visible light catalytic activity decreased with the increase in silver size. Therefore, in order to optimize the Ag-TiO₂ photocatalyst with the lowest pulmonary toxicity and highest catalytic performance, response surface methodology (RSM) was further performed to optimize the two independent variables of AgC and PDT. Visible-light catalytic activity was evaluated by the degradation rate of Rhodamine B, the antibacterial property was evaluated by killing log value for Escherichia coli, and cytotoxicity was evaluated by IC50 to BEAS-2B cells. As a result, the RSM model showed that AgC and PDT exhibited an interaction effect on catalytic activity in the quadratic model. AgC was positively correlated with antibacterial activity. Cytotoxicity was proportional to AgC while inversely proportional to PDT. Finally, the optimization values were AgC 3.08 w/w% and PDT 28 min. Under this optimal condition, the relatively high silver proportion ensured the visible-light catalytic and antibacterial activity, while the longer PDT effectively reduced the cytotoxicity. This study is of significance for the safe and efficient application of silver-doped TiO₂ photocatalysts.

Keywords: Ag-doped TiO₂, cytotoxicity, inflammtion, fibrosis, response surface methodology

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Authors: Puneet Goyal, Aarti Agarwal

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Background and Objective: Nutritional support is an integral part of palliative care of advanced non-resectable abdominal malignancy patients, though is frequently neglected aspect. Non-Healing high output Entero-cutaneous fistulas sometimes require long term parenteral nutrition, to take care of catabolism and replacement of nutrients. We present a case of inoperable pancreatic malignancy with high output entero-cutaneous fistula, which was provided parenteral nutritional support with the use of Totally Implantable Venous Access Device (TIVAD). Method and Results: 55 year old man diagnosed with carcinoma pancreas had developed high entero-cutaneous fistula. His tumor was found to be inoperable and was on total parenteral nutrition through routine central line. This line was difficult to maintain as he required it for a long term TPN. He was planned to undergo Totally Implantable Venous Access Device (TIVAD) implantation. 8Fr single lumen catheter with Groshong non-return Valve (Bard Access Systems, Inc. USA) was inserted through right internal jugular vein, under fluoroscopic guidance. The catheter was tunneled subcutaneously and brought towards infraclavicular pocket, cut at appropriate length and connected to port and locked. Port was sutured in floor of pocket. Free flow of blood aspirated, flushed with heparinized saline. There was no kink observed in entire length of catheter under fluoroscopy. Skin over infraclavicular pocket was sutured. Long term catheter care and associated risks were explained to patient and relatives. Patient continued to receive total parenteral nutrition as well as other supportive therapy though TIVAD for next 6 weeks, till his demise. Conclusion: TIVADs are standard of care for long term venous access solutions in cancer patients requiring chemotherapy. In this case, we extended its use for providing parenteral nutrition and other supportive therapy. TIVADs can be implanted in advanced cancer patients for providing venous access solution required for various palliative treatments and medications. This will help in improving quality of life and satisfaction amongst terminally ill cancer patients.

Keywords: parenteral nutrition, totally implantable venous access device, long term venous access, interventions in anesthesiology

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Authors: Rachel Fanelwa Ajayi, Anovuyo Jonnas, Emmanuel I. Iwuoha

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Tuberculosis (TB) is an infectious disease caused by the bacterium (Mycobacterium tuberculosis) which has a predilection for lung tissue due to its rich oxygen supply. The mycobacterial cell has a unique innate characteristic which allows it to resist human immune systems and drug treatments; hence, it is one of the most difficult of all bacterial infections to treat, let alone to cure. At the same time, multi-drug resistance TB (MDR-TB) caused by poorly managed TB treatment, is a growing problem and requires the administration of expensive and less effective second line drugs which take much longer treatment duration than fist line drugs. Therefore, to acknowledge the issues of patients falling ill as a result of inappropriate dosing of treatment and inadequate treatment administration, a device with a fast response time coupled with enhanced performance and increased sensitivity is essential. This study involved the synthesis of electroactive platforms for application in the development of nano-biosensors suitable for the appropriate dosing of clinically diagnosed patients by promptly quantifying the levels of the TB drug; Isonaizid. These nano-biosensors systems were developed on gold surfaces using the enzyme N-acetyletransferase 2 coupled to the cysteamine modified poly(8-anilino-1-napthalene sulphonic acid)/zinc oxide nanocomposites. The morphology of ZnO nanoparticles, PANSA/ZnO nano-composite and nano-biosensors platforms were characterized using High-Resolution Transmission Electron Microscopy (HRTEM) and High-Resolution Scanning Electron Microscopy (HRSEM). On the other hand, the elemental composition of the developed nanocomposites and nano-biosensors were studied using Fourier Transform Infra-Red Spectroscopy (FTIR) and Energy Dispersive X-Ray (EDX). The electrochemical studies showed an increase in electron conductivity for the PANSA/ZnO nanocomposite which was an indication that it was suitable as a platform towards biosensor development.

Keywords: N-acetyletransferase 2, isonaizid, tuberculosis, zinc oxide

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Authors: E. Isaac, I. Jalo, Y. Alkali, A. Ajani, A. Rasaki, Y. Jibrin, K. Mustapha, A. Ayuba, S. Charanchi, H. Danlami

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Introduction: Hepatitis B infection continues to be a serious global health problem with about 2 billion people infected worldwide, many of these in sub-Saharan Africa. Nigeria is one of the countries with the highest incidence, with a prevalence of 10-15%. Methods: Records of Hepatitis B surface and envelope antigen test results in adults in Federal Teaching Hospital, Gombe between May 2000 and May 2015 were retrieved and analyzed. Findings: Adult out-patient consultations and in-patient admissions were 343,083 and 67,761 respectively, accounting for 87% of total. Hepatitis B surface antigenaemia was tested for in 23,888 adults and children. 88.9% (21240) were adults. Males constituted 56% (11902/21240) and females 44% (9211/21240). 5104 (24.0%) of tested individuals were 19-25years; 12,039 (56.7%) 26-45years; 21119 (9.0%) 46-55years; 2.8% (590/21240) and 766 (3.6%) >65years. Among adult males, 17% (2133/11902) was contributed by ages 19-25. 58% (7017/11902), 11.9% (1421/11902), 6.4% (765/11902) and 4.7% (563/11902) of males were 26-45 years old, 46-55 years old and 56-65 years and >65year old respectively. Adults aged 19-25years, 26-45 years, 46-55years, 56-65 and > 65years each constituted 32% (2966/9211); 54.4% (5009/9211); 7.4% (684/9211), 3.8% (350/9211) and 2.2% (201/9211) of females respectively. 16.2% (3431/21,240) demonstrated Hepatitis B surface antigenaemia. The sero-positivity rate was 16.9% (865//5104) between 19-25years, 21.2% (2559/12,039) among 26-45year old individuals. 17.9% (377/2111); 14.1% (83/590) and 7.3% (56/766) of 46-55year old, 56-65year old and >65year old individuals screened were seropositive. The highest sero-positivity rate was found in male young adults aged 19-25years 27.9% (398/1426) and lowest in elderly males 7.4% (28/377). HBe antigen testing rate among HbSAg seropositive individuals was 97.3% (3338/3431). Males constituted 59.7% (1992/3338) and females 40.3% (1345/3338). 25.3% (844/3338) were aged 19-25years; 61.1% (2039/3338) 26-45years; 10.2% (340/3338) 46-55years; 2.7% (90/3338) 56-65years and 0.7% >65years old. HB e antigenaemia was positive in 8.2% (275/3338) of those tested. 41% (113/275); 50.2% (138/275); 5.4% (15/275); 1.8% (5/275) and 1.1 (3/275) of HB e sero-positivity was among age groups 19-25, 26-45, 46-55, 56-65 and > 65year old individuals. Dual sero-positivity rate was highest 13% (113/844) in young adults 19-25years and lowest between 46-55years; 15/340 (4.4%). 4.2% (15/360); 13.5% (69/512); 6.7% (90/1348); 4.6% (10/214); 5% (2/40) and 6.7% (1/15) of males aged 19-25; 26-45; 46-55; 56-65; and >65years had HB e antigenaemia respectively. Among females - 27/293 (9.2%) aged 19-25; 26/500 (5.2%) 26-45; 2/84 (2.4%) 46-55; 1/12 (8.3%) 56-65 and 1/9(11.1%) >65years had dual antigenaemia. In women of childbearing age, 6.9% (53/793) had a dual carriage. Conclusion: Dual hepatitis B surface and envelope antigenaemia are highest in young adult males. This will have significant implications for the development of chronic liver disease and hepatocellular carcinoma.

Keywords: adult, Hepatitis B, Nigeria, dual carriage

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Authors: Reham H. Soliman, Noha Noufal, Howayda AbdelAal

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Calcium/calmodulin-dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinase (MAGUK) family and has been proposed as a mediator of cell-cell adhesion and proliferation, which can contribute to tumorogenesis. CASK has been linked as a good prognostic factor with some tumor subtypes, while considered as a poor prognostic marker in others. To our knowledge, no sufficient evidence of CASK role in colorectal cancer is available. The aim of this study is to evaluate the expression of Calcium/calmodulin-dependent serine protein kinase (CASK) in non-mucinous colorectal adenocarcinoma and adenomatous polyps as precursor lesions and assess its prognostic significance. The study included 42 cases of conventional colorectal adenocarcinoma and 15 biopsies of adenomatous polyps with variable degrees of dysplasia. They were reviewed for clinicopathological prognostic factors and stained by CASK; mouse, monoclonal antibody using heat-induced antigen retrieval immunohistochemical techniques. The results showed that CASK protein was significantly overexpressed (p <0.05) in CRC compared with adenoma samples. The CASK protein was overexpressed in the majority of CRC samples with 85.7% of cases showing moderate to strong expression, while 46.7% of adenomas were positive. CASK overexpression was significantly correlated with both TNM stage and grade of differentiation (p <0.05). There was a significantly higher expression in tumor samples with early stages (I/II) rather than advanced stage (III/IV) and with low grade (59.5%) rather than high grade (40.5%). Another interesting finding was found among the adenomas group, where the stronger intensity of staining was observed in samples with high grade dysplasia (33.3%) than those of lower grades (13.3%). In conclusion, this study shows that there is significant overexpression of CASK protein in CRC as well as in adenomas with high grade dysplasia. This indicates that CASK is involved in the process of carcinogenesis and functions as a potential trigger of the adenoma-carcinoma cascade. CASK was significantly overexpressed in early stage and low-grade tumors rather than tumors with advanced stage and higher histological grades. This suggests that CASK protein is a good prognostic factor. We suggest that CASK affects CRC in two different ways derived from its physiology. CASK as part of MAGUK family can stimulate proliferation and through its cell membrane localization and as a mediator of cell-cell adhesion might contribute in tumor confinement and localization.

Keywords: CASK, colorectal cancer, overexpression, prognosis

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Authors: Angel Champion

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Chemotherapy and radiation use an acidified approach to induce apoptosis, which only kills mature cancer cells while resulting in gene and cell damage with significant levels of toxicity in tumor-affected tissues and organs. The acid approach, where the cells exterminated are not differentiated, induces the disappearance of white blood cells from the blood. This increases susceptibility to infection in severe forms of cancer spread. However, chemotherapy and radiation cannot kill cancer stem cells that metastasize, being the leading cause of 98% of cancer fatalities. With over 12 million new cancer cases symptomatic each year, including common malignancies such as Hepatocellular Carcinoma (HCC), this study aims to assess the bioactive constituents and phytochemical composition of Taraxacum Officinale (Dandelion). This analysis enables pharmaceutical quality and potency to be applied to studies on cancer cell proliferation and apoptosis. A phytochemical screening is carried out to identify the antioxidant components of Dandelion root, stem, and flower extract. The constituents tested for are phlorotannins, carbohydrates, glycosides, saponins, flavonoids, alkaloids, sterols, triterpenes, and anthraquinone glycosides. To conserve the existing phenolic compounds, a portion of the constituent tests will be examined with an acid, alcohol, or aqueous solvent. As a result, the qualitative and quantitative variations within the Dandelion extract that measure uniform effective potency are vital to the conformity for producing medicinal products. These medicines will be constructed with a consistent, uniform composition that physicians can use to control and effectively eradicate malignant diseases safely. Taraxacum Officinale's phytochemical composition comprises a highly-graded potency due to present bioactive contents that will essentially drive out malignant disease within the human body. Its high potency rate is powerful enough to eliminate both mature cancer cells and cancer stem cells without the cell and gene damage induced by chemotherapy and radiation. Correspondingly, the high margins of cancer mortality on a global scale are mitigated. This remarkable contribution to modern therapeutics will essentially optimize the margins of natural products and their derivatives, which account for 50% of pharmaceuticals in modern therapeutics, while preventing the adverse effects of radiation and chemotherapy drugs.

Keywords: antioxidant, apoptosis, metastasize, phytochemical, proliferation, potency

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Authors: Zakaria Baka, Halima Alem

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Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.

Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques

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Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

Abstract:

MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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