Search results for: cancer recovery

Authors: Loren S. Bernal., Catalina Castillo, Carel E. Carvajal, José F. Ibla

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Plastic pollution, specifically microplastics, has become a significant issue in aquatic ecosystems worldwide. The large amount of plastic waste carried by water tributaries has resulted in the accumulation of microplastics in water bodies. The polymer aging process caused by environmental influences such as photodegradation and chemical degradation of additives leads to polymer embrittlement and properties change that require degradation or reduction procedures in rivers. However, there is a lack of such procedures for freshwater entities that develop over extended periods. The aim of this study is evaluate the potential of Pleurotus ostreatus a fungus, in reducing lowdensity polyethylene microplastics present in freshwater samples collected from the middle basin of the Magdalena River in Colombia. The study aims to evaluate this process both in vitro and in silico by identifying the growth capacity of Pleurotus ostreatus in the presence of microplastics and identifying the most likely interactions of Pleurotus ostreatus enzymes and their affinity energies. The study follows an engineering development methodology applied on an experimental basis. The in vitro evaluation protocol applied in this study focused on the growth capacity of Pleurotus ostreatus on microplastics using enzymatic inducers. In terms of in silico evaluation, molecular simulations were conducted using the Autodock 1.5.7 program to calculate interaction energies. The molecular dynamics were evaluated by using the myPresto Portal and GROMACS program to calculate radius of gyration and Energies.The results of the study showed that Pleurotus ostreatus has the potential to degrade low-density polyethylene microplastics. The in vitro evaluation revealed the adherence of Pleurotus ostreatus to LDPE using scanning electron microscopy. The best results were obtained with enzymatic inducers as a MnSO4 generating the activation of laccase or manganese peroxidase enzymes in the degradation process. The in silico modelling demonstrated that Pleurotus ostreatus was able to interact with the microplastics present in LDPE, showing affinity energies in molecular docking and molecular dynamics shown a minimum energy and the representative radius of gyration between each enzyme and its substract. The study contributes to the development of bioremediation processes for the removal of microplastics from freshwater sources using the fungus Pleurotus ostreatus. The in silico study provides insights into the affinity energies of Pleurotus ostreatus microplastic degrading enzymes and their interaction with low-density polyethylene. The study demonstrated that Pleurotus ostreatus can interact with LDPE microplastics, making it a good agent for the development of bioremediation processes that aid in the recovery of freshwater sources. The results of the study suggested that bioremediation could be a promising approach to reduce microplastics in freshwater systems.

Keywords: bioremediation, in silico modelling, microplastics, Pleurotus ostreatus

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Authors: Sree Sanyal

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Research in ageing often highlights the age-related health dimension more than the psycho-social characteristics of the elderly, which also influences and challenges the health outcomes. Multimorbidity is defined as the person having more than one chronic non-communicable diseases and their prevalence increases with ageing. The study aims to evaluate the influence of social ties on self-reported prevalence of multimorbidity (selected chronic non-communicable diseases) among the selected states of elderly population in India. The data is accessed from Building Knowledge Base on Population Ageing in India (BKPAI), collected in 2011 covering the self-reported chronic non-communicable diseases like arthritis, heart disease, diabetes, lung disease with asthma, hypertension, cataract, depression, dementia, Alzheimer’s disease, and cancer. The data of the above diseases were taken together and categorized as: ‘no disease’, ‘one disease’ and ‘multimorbidity’. The predicted variables were demographic, socio-economic, residential types, and the variable of social ties includes social support, social engagement, perceived support, connectedness, and importance of the elderly. Predicted probability for multiple logistic regression was used to determine the background characteristics of the old in association with chronic morbidities showing multimorbidity. The finding suggests that 24.35% of the elderly are suffering from multimorbidity. Research shows that with reference to ‘no disease’, according to the socio-economic characteristics of the old, the female oldest old (80+) from others in caste and religion, widowed, never had any formal education, ever worked in their life, coming from the second wealth quintile standard, from rural Maharashtra are more prone with ‘one disease’. From the social ties background, the elderly who perceives they are important to the family, after getting older their decision-making status has been changed, prefer to stay with son and spouse only, satisfied with the communication from their children are more likely to have less single morbidity and the results are significant. Again, with respect to ‘no disease’, the female oldest old (80+), who are others in caste, Christian in religion, widowed, having less than 5 years of education completed, ever worked, from highest wealth quintile, residing in urban Kerala are more associated with multimorbidity. The elderly population who are more socially connected through family visits, public gatherings, gets support in decision making, who prefers to spend their later years with son and spouse only but stays alone shows lesser prevalence of multimorbidity. In conclusion, received and perceived social integration and support from associated neighborhood in the older days, knowing about their own needs in life facilitates better health and wellbeing of the elderly population in selected states of India.

Keywords: morbidity, multi-morbidity, prevalence, social ties

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Authors: Babarina Maria, Andropova Margarita

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Introduction: Hypoparathyroidism (HypoPT) is a rare endocrine disorder with an estimated prevalence of 0.25 per 1000 individuals. The most common cause of HypoPT is the loss of active parathyroid tissue following thyroid or parathyroid surgery. Sometimes permanent postoperative HypoPT occures, manifested by hypocalcemia in combination with low levels of PTH during 6 months or more after surgery. Cognitive impairments in patients with hypocalcemia due to chronic HypoPT are observed, and this can lead to problems and challenges in everyday living: memory loss and impaired concentration, that may be the cause of poor compliance. Clinical case: Patient K., 66 years old, underwent thyroidectomy in 2013 (at the age of 55) because of papillary thyroid cancer T1NxMx, histopathology findings confirmed the diagnosis. 5 years after the surgery, she was followed up on an outpatient basis, TSH levelsonly were monitored, and the dose of levothyroxine was adjusted. In 2018 due to, increasing complaints include tingling and cramps in the arms and legs, memory loss, sleep disorder, fatigue, anxiety, hair loss, muscle pain, tachycardia, positive Chvostek, and Trousseau signs were diagnosed during examination, also in blood analyses: total Ca 1.86 mmol/l (2.15-2.55), Ca++ 0.96 mmol/l (1.12-1.3), P 1.55 mmol/l (0.74-1.52), Mg 0.79 mmol/l (0.66-1.07) - chronic postoperative HypoPT was diagnosed. Therapy was initiated: alfacalcidol 0.5 mcg per day, calcium carbonate 2000 mg per day, cholecalciferol 1000 IU per day, magnesium orotate 3000 mg per day. During the case follow-up, hypocalcemia, hyperphosphatemia persisted, hypercalciuria15.7 mmol/day (2.5-6.5) was diagnosed. Dietary recommendations were given because of the high content of phosphorus rich foods, and therapy was adjusted: the dose of alfacalcidol was increased to 2.5 mcg per day, and the dose of calcium carbonate was reduced to 1500 mg per day. As part of the screening for complications of hypoPT, data for cataracts, Fahr syndrome, nephrocalcinosis, and kidney stone disease were not obtained. However, HypoPT compensation was not achieved, and therefore hydrochlorothiazide 25 mg was initiated, the dose of alfacalcidol was increased to 3 mcg per day, calcium carbonate to 3000 mg per day, magnesium orotate and cholecalciferol were continued at the same doses. Therapeutic goals were achieved: calcium phosphate product <4.4 mmol2/l2, there were no episodes of hypercalcemia, twenty-four-hour urinary calcium excretion was significantly reduced. Conclusion: Timely prescription, careful explanation of drugs usage rules, and monitoring and maintaining blood and urine parameters within the target contribute to the prevention of HypoPT complications development and life-threatening events.

Keywords: hypoparathyroidism, hypocalcemia, hyperphosphatemia, hypercalciuria

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Authors: Sadi Ali, Yaser Kishawi

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As part of Palestine, Gaza Strip (365 km2 and 1.8 million habitants) is considered a semi-arid zone relies solely on the Coastal Aquifer. The coastal aquifer is only source of water with only 5-10% suitable for human use. This barely cover the domestic and agricultural needs of Gaza Strip. Palestinian Water Authority Strategy is to find non-conventional water resource from treated wastewater to irrigate 1500 hectares and serves over 100,000 inhabitants. A new WWTP project is to replace the old-overloaded Biet Lahia WWTP. The project consists of three parts; phase A (pressure line & 9 infiltration basins - IBs), phase B (a new WWTP) and phase C (Recovery and Reuse Scheme – RRS – to capture the spreading plume). Currently, phase A is functioning since Apr 2009. Since Apr 2009, a monitoring plan is conducted to monitor the infiltration rate (I.R.) of the 9 basins. Nearly 23 million m3 of partially treated wastewater were infiltrated up to Jun 2014. It is important to maintain an acceptable rate to allow the basins to handle the coming quantities (currently 10,000 m3 are pumped an infiltrated daily). The methodology applied was to review and analysis the collected data including the I.R.s, the WW quality and the drying-wetting schedule of the basins. One of the main findings is the relation between the Total Suspended Solids (TSS) at BLWWTP and the I.R. at the basins. Since April 2009, the basins scored an average I.R. of about 2.5 m/day. Since then the records showed a decreasing pattern of the average rate until it reached the lower value of 0.42 m/day in Jun 2013. This was accompanied with an increase of TSS (mg/L) concentration at the source reaching above 200 mg/L. The reducing of TSS concentration directly improved the I.R. (by cleaning the WW source ponds at Biet Lahia WWTP site). This was reflected in an improvement in I.R. in last 6 months from 0.42 m/day to 0.66 m/day then to nearly 1.0 m/day as the average of the last 3 months of 2013. The wetting-drying scheme of the basins was observed (3 days wetting and 7 days drying) besides the rainfall rates. Despite the difficulty to apply this scheme accurately a control of flow to each basin was applied to improve the I.R. The drying-wetting system affected the I.R. of individual basins, thus affected the overall system rate which was recorded and assessed. Also the ploughing activities at the infiltration basins as well were recommended at certain times to retain a certain infiltration level. This breaks the confined clogging layer which prevents the infiltration. It is recommended to maintain proper quality of WW infiltrated to ensure an acceptable performance of IBs. The continual maintenance of settling ponds at BLWWTP, continual ploughing of basins and applying soil treatment techniques at the IBs will improve the I.R.s. When the new WWTP functions a high standard effluent quality (TSS 20mg, BOD 20 mg/l and TN 15 mg/l) will be infiltrated, thus will enhance I.R.s of IBs due to lower organic load.

Keywords: SAT, wastewater quality, soil remediation, North Gaza

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Authors: Eszter Repasi, Akos Koller

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Our genetic information determines our look, physiology, sports performance and all our features. Maximizing the performances of athletes have adopted a science-based approach to the nutritional support. Nowadays genetics studies have blended with nutritional sciences, and a dynamically evolving, new research field have appeared. Nutritional genomics is needed to be used by nutritional experts. This is a recent field of nutritional science, which can provide a solution to reach the best sport performance using correlations between the athlete’s genome, nutritions, molecules, included human microbiome (links between food, microbiome and epigenetics), nutrigenomics and nutrigenetics. Nutritional genomics has a tremendous potential to change the future of dietary guidelines and personal recommendations. Experts need to use new technology to get information about the athletes, like nutritional genomics profile (included the determination of the oral and gut microbiome and DNA coded reaction for food components), which can modify the preparation term and sports performance. The influence of nutrients on the genes expression is called Nutrigenomics. The heterogeneous response of gene variants to nutrients, dietary components is called Nutrigenetics. The human microbiome plays a critical role in the state of health and well-being, and there are more links between food or nutrition and the human microbiome composition, which can develop diseases and epigenetic changes as well. A nutritional genomics-based profile of athletes can be the best technic for a dietitian to make a unique sports nutrition diet plan. Using functional food and the right food components can be effected on health state, thus sports performance. Scientists need to determine the best response, due to the effect of nutrients on health, through altering genome promote metabolites and result changes in physiology. Nutritional biochemistry explains why polymorphisms in genes for the absorption, circulation, or metabolism of essential nutrients (such as n-3 polyunsaturated fatty acids or epigallocatechin-3-gallate), would affect the efficacy of that nutrient. Controlled nutritional deficiencies and failures, prevented the change of health state or a newly discovered food intolerance are observed by a proper medical team, can support better sports performance. It is important that the dietetics profession informed on gene-diet interactions, that may be leading to optimal health, reduced risk of injury or disease. A special medical application for documentation and monitoring of data of health state and risk factors can uphold and warn the medical team for an early action and help to be able to do a proper health service in time. This model can set up a personalized nutrition advice from the status control, through the recovery, to the monitoring. But more studies are needed to understand the mechanisms and to be able to change the composition of the microbiome, environmental and genetic risk factors in cases of athletes.

Keywords: gene-diet interaction, multidisciplinary team, microbiome, diet plan

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Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

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Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

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Authors: Sharad Kumar Kulshreshtha

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India is a great land of cultural and traditional diversity. Its spectrums create a unique ambiance in all over the country. Specially, fairs and festivals are ancient phenomena in Indian culture. In India, there are thousands of such religious, spiritual, cultural fairs organized on auspicious occasions. These fairs reflect the effective and efficient role of social governance and responsibility of Indian society. In this context a mega event known as ‘Kumbha Mela’ literally mean ‘Kumbha Fair’ which is organize after every twelve years at (Prayaag) Allahabad an ancient city of India, now is in the state of Uttar Pradesh. Kumbh Mela is one of the largest human congregations on the Earth. The Kumbha Mela that is held here is considered to be the largest and holiest city among the four cities where Kubha fair organize. According to the Hindu religious scripture a dip for possessing the holy confluence, known as Triveni Sangam, which is a meeting point of the three sacred rivers of India i.e., –Ganges, Yamuna and Saraswati (mythical). During the Kumbha fair the River Ganges is believed to turn to nectar, bringing great blessing to everyone who bathes in it. Other activities include religious discussions, devotional singings and mass feedings pilgrims and poor. The venue for Kumbh Mela (fair) depends on the position Sun, Moon, and Jupiter which holds in that period in different zodiac signs. More than 120 Millions (12 Crore) people visited in the Kumbha Fair-2013 in Allahabad. A temporary tented city was set up for the pilgrims over an area of 2 hectares of the land along the river of Ganges. As many as 5 power substations, temporary police stations, hospitals, bus terminals, stalls were set up for providing various facilities to the visitors and thousands of volunteers participated for assistance of this event. All efforts made by fair administration to provide facility to visitors, such security and sanitation, medical care and frequent water and power supply. The efficient and timely arrangement at the Kumbha Mela attracted the attention of many government and institutions. The Harvard University of USA conducted research to find out how it was made possible. This paper will focuses on effective and efficient planning and preparation of Kumbha Fair which includes facilitation process, role of various coordinating agencies. risk management crisis management strategies Prevention, Preparedness, Response, and Recovery (PPRR Approach), emergency response plan (ERP), safety and security issues, various environmental aspects along with health hazards and hygiene crowd management, evacuation, monitoring, control and evaluation.

Keywords: event planning and facility arrangement, risk management, crowd management, India

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Authors: Valeria Cotza

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School drop-out is a multifactorial phenomenon that in Italy concerns all those underage students who, at different school stages (up to 16 years old) or training (up to 18 years old), manifest educational difficulties from dropping out of compulsory education without obtaining a qualification to repetition rates and absenteeism. From the 1980s to the 2000s, there was a progressive attenuation of the economic and social model towards a multifactorial reading of the phenomenon, and the European Commission noted the importance of learning about the phenomenon through approaches able to integrate large-scale quantitative surveys with qualitative analyses. It is not a matter of identifying the contextual factors affecting the phenomenon but problematising them by means of systemic and comprehensive in-depth analysis. So, a privileged point of observation and field of intervention are those schools that propose alternative models of teaching and learning to the traditional ones, such as popular and second-chance schools. Alternative schools and interventions grew in these years in Europe as well as in the US and Latin America, working in the direction of greater equity to create the conditions (often absent in conventional schools) for everyone to achieve educational goals. Against extensive Anglo-Saxon and US literature on this topic, there is yet no unambiguous definition of alternative education, especially in Europe, where second-chance education has been most studied. There is little literature on a second chance in Italy and almost none on alternative education (with the exception of method schools, to which in Italy the concept of “alternative” is linked). This research aims to fill the gap by systematically surveying the alternative interventions in the area and beginning to explore some models of popular and second-chance schools and experiences through a mixed methods approach. So, the main research objectives concern the spread of alternative education in the Lombardy region, the main characteristics of these schools and interventions, and their effectiveness in terms of students’ well-being and school results. This paper seeks to answer the first point by presenting the preliminary results of the first phase of the project dedicated to mapping. Through the Google Forms platform, a questionnaire is being distributed to all schools in Lombardy and some schools in the rest of Italy to map the presence of alternative schools and interventions and their main characteristics. The distribution is also taking place thanks to the support of the Milan Territorial and Lombardy Regional School Offices. Moreover, other social realities outside the school system (such as cooperatives and cultural associations) can be questioned. The schools and other realities to be questioned outside Lombardy will also be identified with the support of INDIRE (Istituto Nazionale per Documentazione, Innovazione e Ricerca Educativa, “National Institute for Documentation, Innovation and Educational Research”) and based on existing literature and the indicators of “Futura” Plan of the PNRR (Piano Nazionale di Ripresa e Resilienza, “National Recovery and Resilience Plan”). Mapping will be crucial and functional for the subsequent qualitative and quantitative phase, which will make use of statistical analysis and constructivist grounded theory.

Keywords: school drop-out, alternative education, popular and second-chance schools, map

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Authors: Norazlan Mohmad Misnan, Maizatul Hasyima Omar, Mohd Isa Wasiman

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Papaya (Carica papaya L., Caricaceae) is a tree which mainly cultivated for its fruits in many tropical regions including Australia, Brazil, China, Hawaii, and Malaysia. Beside of fruits, its leaves, seeds, and latex have also been traditionally used for treating diseases, which also reported to possess anti-cancer and anti- malaria properties. Its leaves have been reported to consist of various chemical compounds such as alkaloids, flavonoids and phenolics. Clitorin and manghaslin are among major flavonoids presence. Thus, the aim of this study is to quantify the purity of these isolated compounds (clitorin and manghsalin) by using quantitative Nuclear Magnetic Resonance (qNMR) analysis. Only fresh C. papaya leaves were used for juice extraction procedure and subsequently was freeze-dried to obtain a dark green powdered form of the extract prior to Centrifugal Partition Chromatography (CPC) separation. The CPC experiments were performed using a two-phase solvent system comprising ethyl acetate/butanol/water (1:4:5, v/v/v/v) solvent. The upper organic phase was used as the stationary phase, and the lower aqueous phase was employed as the mobile phase. Ten fractions were obtained after an hour runtime analysis. Fraction 6 and fraction 8 has been identified as clitorin (m/z 739.21 [M-H]-) and manghaslin (m/z 755.21 [M-H]-), respectively, based on LCMS data and full analysis of NMR (1H NMR, 13C NMR, HMBC, and HSQC). The 1H-qNMR measurements were carried out using a 400 MHz NMR spectrometer (JEOL ECS 400MHz, Japan) and deuterated methanol was used as a solvent. Quantification was performed using the AQARI method (Accurate Quantitative NMR) with deuterated 1,4-Bis(trimethylsilyl)benzene (BTMSB) as an internal reference substances. This AQARI protocol includes not only NMR measurement but also sample preparation that provide highest precision and accuracy than other qNMR methods. The 90° pulse length and the T1 relaxation times for compounds and BTMSB were determined prior to the quantification to give the best signal-to-noise ratio. Regions containing the two downfield signals from aromatic part (6.00–6.89 ppm), and the singlet signal, (18H) arising from BTMSB (0.63-1.05ppm) were selected for integration. The purity of clitorin and manghaslin were calculated to be 52.22% and 43.36%, respectively. Further purification is needed in order to increase its purity. This finding has demonstrated the use of qNMR for quality control and standardization of various plant extracts and which can be applied for NMR fingerprinting of other plant-based products with good reproducibility and in the case where commercial standards is not readily available.

Keywords: Carica papaya, clitorin, manghaslin, quantitative Nuclear Magnetic Resonance, Centrifugal Partition Chromatography

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Authors: I. Brezeanu, J. Mackrill, A. Cajo, C. Mogollon

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Modern Slavery is a serious crime, where often the victims are unable to leave their situation of exploitation, being controlled by threats, punishment, violence, coercion, and deception. In the UK, this term encompasses both Slavery and Human Trafficking. The number of potential victims who were referred to the National Referral Mechanism (NRM) increased exponentially in the past decade, passing from fewer than 700 potential victims referred in 2010 to more than 12.000 in 2021. Our study aims to explore how the concept of Trauma-Informed Care (TIC) approach can be adopted by services working with survivors of Modern Slavery and Trafficking (MST). Notably, in this paper, we will elaborate on how the complex needs of survivors are related to their traumatic experiences and what are the necessary steps and resources for implementing a Modern Slavery Trauma-Informed model. While there are relatively few services in the UK that have a deep understanding of the survivors’ and practitioners’ views of how trauma impacts their daily life, there is a strong need for developing services that are organised and delivered in ways that prevent retraumatisation and enable trauma survivors to engage safely with the right professionals at the right time, promoting healing through positive relationships. Such models, known as Trauma-Informed Approaches (TIAs), are seen as crucial to the empowerment of survivors, yet they remain a marginal implementation model by governments, law enforcement, judiciary, or care providers, who are frequently survivors’ first point of contact in the recovery process. In order to understand better how to provide best practice and to adopt the concept, this study is based on a multi-disciplinary approach, encompassing both theoretical perspectives and co-production. By combining qualitative and quantitative research and comparing different analysis of applied examples of TIC in the US and the UK, we gained important insights about the prevention and impact of trauma on survivors’ life. The articulation between more general expertise on Trauma-Informed Care developed by other institutions operating in the field, and the SJOG delivery, based on the Salvation Army’s Modern Slavery Victim Care and Coordination Contract (MSVCC) and the Care Quality Commission regulations, allowed to identify on one side what are the complex needs of survivors derived from their traumatic experiences, and on the other side, how could MST services prevent retraumatisation. Additional, two in-depth interviews with survivors, who receive support from one of our services at Olallo House in London, and a survey shared among all colleagues working with MST services completed the findings of the research with their personal experience and knowledge. Ultimately, we developed an evidence-based Trauma-Informed Care Pathway that aims to improve the wellbeing of survivors and to support them to live a meaningful life. The establishedpathway delivers three main outcomes belonging to the social determinants of health criteria – health and wellbeing, purpose and relationship, and covers key themes of the context of trauma, needs of individuals, and service support.

Keywords: trauma-informed care, modern slavery, human trafficking, trauma, retraumatisation

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Authors: Dalita G. S. M. Cavalcante, Elton A. P. dos Reis, Andressa S. Gomes, Caroline S. Danna, Leandra Ernest Kerche-Silva, Eidi Yoshihara, Aldo E. Job

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In order to minimize environmental impacts, a composite was developed from mixture of leather shavings (LE) with natural rubber (NR), which patent is already deposited. The new material created can be used in applications such as floors e heels for shoes. Besides these applications, the aim is to use this new material for the production of products for the textile industry, such as boots, gloves and bags. But the question arises, as to biocompatibility of this new material. This is justified because the structure of the leather shavings has chrome. The trivalent chromium is usually not toxic, but the hexavalent chromium can be highly toxic and genotoxic for living beings, causing damage to the DNA molecule and contributing to the formation of cancer. Based on this, the objective of this study is evaluate the possible genotoxic effects of the new composite, using as system - test two cell lines (MRC-5 and CHO-K1) by comet assay. For this, the production of the composite was performed in three proportions: for every 100 grams of NR was added 40 (E40), 50 (E50) or 60 (E60) grams of LE. The latex was collected from the rubber tree (Hevea brasiliensis). For vulcanization of the NR, activators and accelerators were used. The two cell lines were exposed to the new composite in its three proportions using elution method, that is, cells exposed to liquid extracts obtained from the composite for 24 hours. For obtaining the liquid extract, each sample of the composite was crushed into pieces and mixed with an extraction solution. The quantification of total chromium and hexavalent chromium in the extracts were performed by Optical Emission Spectrometry by Inductively Coupled Plasma (ICP-OES). The levels of DNA damage in cells exposed to both extracts were monitored by alkaline version of the comet assay. The results of the quantification of metals in ICP-OES indicated the presence of total chromium in different extracts, but were not detected presence of hexavalent chromium in any extract. Through the comet assay were not found DNA damage of the CHO-K1 cells exposed to both extracts. As for MRC-5, was found a significant increase in DNA damage in cells exposed to E50 and E60. Based on the above data, it can be asserted that the extracts obtained from the composite were highly genotoxic for MRC-5 cells. These biological responses do not appear to be related to chromium metal, since there was a predominance of trivalent chromium in the extracts, indicating that during the production process of the new composite, there was no formation of hexavalent chromium. In conclusion it can infer that the leather shavings containing chromium can be reused, thereby reducing the environmental impacts of this waste. Already on the composite indicates to its incorporation in applications that do not aim at direct contact with the human skin, and it is suggested the chain of composite production be studied, in an attempt to make it biocompatible so that it may be safely used by the textile industry.

Keywords: cell line, chrome, genotoxicity, leather, natural rubber

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Authors: Zahide Tepeli Temiz, Itir Tari Comert

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Attachment patterns based on early emotional interactions between infant and primary caregiver continue to be influential in adult life, in terms of mental health and behaviors of individuals. Several studies reveal that infant-caregiver relationships have impressed the affect regulation, coping with stressful and negative situations, general satisfaction of life, and self image in adulthood, besides the attachment styles. The present study aims to examine the relationships between university students’ attachment style and their self-esteem, alexithymic features, satisfaction of life, and level of resilience. In line with this aim, the hypothesis of the prediction of attachment styles (anxious and avoidant) over life satisfaction, self-esteem, alexithymia, and psychological resilience was tested. Additionally, in this study Structural Equational Modeling was conducted to investigate the mediational role of self-esteem in the relationship between attachment styles and alexithymia, life satisfaction, and resilience. This model was examined with path analysis. The sample of the research consists of 425 university students who take education from several region of Turkey. The participants who sign the informed consent completed the Demographic Information Form, Experiences in Close Relationships-Revised, Rosenberg Self-Esteem Scale, The Satisfaction with Life Scale, Toronto Alexithymia Scale, and Resilience Scale for Adults. According to results, anxious, and avoidant dimensions of insecure attachment predicted the self-esteem score and alexithymia in positive direction. On the other hand, these dimensions of attachment predicted life satisfaction in negative direction. The results of linear regression analysis indicated that anxious and avoidant attachment styles didn’t predict the resilience. This result doesn’t support the theory and research indicating the relationship between attachment style and psychological resilience. The results of path analysis revealed the mediational role self esteem in the relation between anxious, and avoidant attachment styles and life satisfaction. In addition, SEM analysis indicated the indirect effect of attachment styles over alexithymia and resilience besides their direct effect. These findings support the hypothesis of this research relation to mediating role of self-esteem. Attachment theorists suggest that early attachment experiences, including supportive and responsive family interactions, have an effect on resilience to harmful situations in adult life, ability to identify, describe, and regulate emotions and also general satisfaction with life. Several studies examining the relationship between attachment styles and life satisfaction, alexithymia, and psychological resilience draw attention to mediational role of self-esteem. Results of this study support the theory of attachment patterns with the mediation of self-image influence the emotional, cognitive, and behavioral regulation of person throughout the adulthood. Therefore, it is thought that any intervention intended for recovery in attachment relationship will increase the self-esteem, life satisfaction, and resilience level, on the one side, decrease the alexithymic features, on the other side.

Keywords: alexithymia, anxious attachment, avoidant attachment, life satisfaction, path analysis, resilience, self-esteem, structural equation

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Authors: Patrícia Pires, Renata Vaz, Bárbara Teles, Marco Pato, Pedro Beckert

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Introduction: The management of lateral third clavicle fractures can be challenging due to difficulty in distinguishing subtle variations in the fracture pattern, which may be suggestive of potential fracture instability. They occur most often in men between 30 and 50 years of age, and in individuals over 70 years of age, its distribution is equal between both men and women. These fractures account for 10%–30% of all clavicle fractures and roughly 30%–45% of all clavicle nonunion fractures. Lateral third clavicle fractures may be treated conservatively or surgically, and there is no gold standard, although the risk of nonunion or pseudoarthrosis impacts the recommendation of surgical treatment when these fractures are unstable. There are many strategies for surgical treatment, including locking plates, hook plates fixation, coracoclavicular fixation using suture anchors, devices or screws, tension band fixation with suture or wire, transacromial Kirschner wire fixation and arthroscopically assisted techniques. Whenever taking the hardware into consideration, we must not disregard that obtaining adequate lateral fixation of small fragments is a difficult task, and plates are more associated to local irritation. The aim of the appropriate treatment is to ensure fracture healing and a rapid return to preinjury activities of daily living but, as explained, definitive treatment strategies have not been established and the variety of techniques avalilable add up to the discussion of this topic. Methods and Results: We present a clinical case of a 43-year-old man with the diagnosis of a lateral third clavicle fracture (Neer IIC) in the sequence of a fall on his right shoulder after a bicycle fall. He was operated three days after the injury, and through K-wire temporary fixation and indirect reduction using a ZipTight, he underwent osteosynthesis with an interfragmentary figure-of-eight tension band with polydioxanone suture (PDS). Two weeks later, there was a good aligment. He kept the sling until 6 weeks pos-op, avoiding efforts. At 7-weeks pos-op, there was still a good aligment, starting the physiotherapy exercises. After 10 months, he had no limitation in mobility or pain and returned to work with complete recovery in strength. Conclusion: Some distal clavicle fractures may be conservatively treated, but it is widely accepted that unstable fractures require surgical treatment to obtain superior clinical outcomes. In the clinical case presented, the authors chose an osteosuture technique due to the fracture pattern, its location. Since there isn´t a consensus on the prefered fixation method, it is important for surgeons to be skilled in various techniques and decide with their patient which approach is most appropriate for them, weighting the risk-benefit of each method. For instance, with the suture technique used, there is no wire migration or breakage, and it doesn´t require a reoperation for hardware removal; there is also less tissue exposure since it requires a smaller approach in comparison to the plate fixation and avoids cuff tears like the hook plate. The good clinical outcome on this case report serves the purpose of expanding the consideration of this method has a therapeutic option.

Keywords: lateral third, clavicle, suture, fixation

Procedia PDF Downloads 43

Authors: Maryam Nazari

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COVID-19 is a respiratory disease triggered by the novel coronavirus, SARS-CoV-2, that has reached pandemic status today. Acute inflammation and immune cells infiltration into lung injuries result in multi-organ failure. The presence of other non-communicable diseases (NCDs) with systemic inflammation derived from COVID-19 may exacerbate the patient's situation and increase the risk for adverse effects and mortality. This pandemic is a novel situation and the scientific community at this time is looking for vaccines or drugs to treat the pathology. One of the biggest challenges is focused on reducing inflammation without compromising the correct immune response of the patient. In this regard, addressing the nutritional factors should not be overlooked not only as a matter of avoiding the presence of NCDs with severe infections but also as an adjunctive way to modulate the inflammatory status of the patients. Despite the pivotal role of nutrition in modifying immune response, due to the novelty of the COVID-19 disease, information about the effects of specific dietary agents is limited in this area. From the macronutrients point of view, protein deficiency (quantity or quality) has negative effects on the number of functional immunoglobulins and gut-associated lymphoid tissue (GALT). High biological value proteins or some amino acids like arginine and glutamine are well known for their ability to augment the immune system. Among lipids, fish oil has the ability to inactivate enveloped viruses, suppress pro-inflammatory prostaglandin production and block platelet-activating factors and their receptors. In addition, protectin D1, which is an Omega-3 PUFAs derivation, is a novel antiviral drug. So it seems that these fatty acids can reduce the severity and/or improve recovery of patients with COVID-19. Carbohydrates with lower glycemic index and fibers are associated with lower levels of inflammatory cytokines (CRP, TNF-α, and IL-6). Short-Chain Fatty acids not only exert a direct anti-inflammatory effect but also provide appropriate gut microbial, which is important in gastrointestinal issues related to COVID-19. From the micronutrients point of view, Vitamins A, C, D, E, iron, magnesium, zinc, selenium and copper play a vital role in the maintenance of immune function. Inadequate status in these nutrients may result in decreased resistance against COVID-19 infection. There are specific bioactive compounds in the diet that interact with the ACE2 receptor, which is the gateway for SARS and SARS-CoV-2, and thus controls the viral infection. Regarding this, the potential benefits of probiotics, resveratrol (a polyphenol found in grape), oleoylethanolamide (derived from oleic acid), and natural peroxisome proliferator-activated receptor γ agonists in foodstuffs (like curcumin, pomegranate, hot pepper) are suggested. Yet, it should be pointed out that most of these results have been reported in animal models and further human studies are needed to be verified.

Keywords: Covid-19, inflammation, nutrition, dietary agents

Procedia PDF Downloads 148

Authors: Gustavo Axel Elizalde-Velázquez

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Metformin is the first line of oral therapy to treat type II diabetes and is also employed as a treatment for other indications, such as polycystic ovary syndrome, cancer, and COVID-19. Recent data suggest it is the aspirin of the 21st century due to its antioxidant and anti-aging effects. However, increasingly current articles indicate its long-term consumption generates mitochondrial impairment. Up to date, it is known metformin increases the biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, but further information related to brain damage after its consumption is missing. Bearing in mind the above, this work aimed to establish whether or not chronic exposure to metformin may alter swimming behavior and induce neurotoxicity in Danio rerio adults. For this purpose, 250 Danio rerio grown-ups were assigned to six tanks of 50 L of capacity. Four of the six systems contained 50 fish, while the remaining two had 25 fish (≈1 male:1 female ratio). Every system with 50 fish was allocated one of the three metformin treatment concentrations (1, 20, and 40 μg/L), with one system as the control treatment. Systems with 25 fish, on the other hand, were used as positive controls for acetylcholinesterase (10 μg/L of Atrazine) and oxidative stress (3 μg/L of Atrazine). After four months of exposure, a mean of 32 fish (S.D. ± 2) per group of MET treatment survived, which were used for the evaluation of behavior with the Novel Tank test. Moreover, after the behavioral assessment, we aimed to collect the blood and brains of all fish from all treatment groups. For blood collection, fish were anesthetized with an MS-222 solution (150 mg/L), while for brain gathering, fish were euthanized using the hypothermic shock method (2–4 °C). Blood was employed to determine CASP3 activity and the percentage of apoptotic cells with the TUNEL assay, and brains were used to evaluate acetylcholinesterase activity, oxidative damage, and gene expression. After chronic exposure, MET-exposed fish exhibited less swimming activity when compared to control fish. Moreover, compared with the control group, MET significantly inhibited the activity of AChE and induced oxidative damage in the brain of fish. Concerning gene expression, MET significantly upregulated the expression of Nrf1, Nrf2, BAX, p53, BACE1, APP, PSEN1, and downregulated CASP3 and CASP9. Although MET did not overexpress the CASP3 gene, we saw a meaningful rise in the activity of this enzyme in the blood of fish exposed to MET compared to the control group, which we then confirmed by a high number of apoptotic cells in the TUNEL assay. To the best of our understanding, this is the first study that delivers evidence of oxidative impairment, apoptosis, AChE alteration, and overexpression of B- amyloid-related genes in the brain of fish exposed to metformin.

Keywords: AChE inhibition, CASP3 activity, NovelTank test, oxidative damage, TUNEL assay

Procedia PDF Downloads 57

Authors: Vanessa Bennemann, Gabriela Laste, Márcia Inês Goettert

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The gestational period is a phase in which the pregnant woman undergoes constant physiological and hormonal changes, which are part of the woman’s biological cycle, the development of the fetus, childbirth, and lactation. These are factors of response to the immunological adaptation of the human reproductive process that is directly related to the pregnancy’s well-being and development. Although most pregnancies occur without complications, about 15% of pregnant women will develop potentially fatal complications, implying maternal and fetal risk. Therefore, requiring specialized care for high-risk pregnant women (HRPW) with obstetric interventions for the survival of the mother and/or fetus. Among the risk factors that characterize HRPW are the women's age, gestational diabetes mellitus (GDM), autoimmune diseases, infectious diseases such as syphilis and HIV, hypertension (SAH), preeclampsia, eclampsia, HELLP syndrome, uterine contraction abnormalities, and premature placental detachment (PPD), thyroid disorders, among others. Thus, pregnancy has an impact on the thyroid gland causing changes in the functioning of the mother's thyroid gland, altering the thyroid hormone (TH) profiles and production as pregnancy progresses. Considering, throughout the gestational period, the interpretation of the results of the tests to evaluate the thyroid functioning depends on the stage in which the pregnancy is. Thyroid disorders are directly related to adverse obstetric outcomes and in child development. Therefore, the adequate release of TH is important for a pregnancy without complications and optimal fetal growth and development. Objective: Investigate the physiological effects caused by thyroid disorders in the gestational period. Methods: A search for articles indexed in PubMed, Scielo, and MDPI databases, was performed using the term “AND”, with the descriptors: Pregnancy, Thyroid. With several combinations that included: Melatonin, Thyroidopathy, Inflammatory processes, Cytokines, Anti-inflammatory, Antioxidant, High-risk pregnancy. Subsequently, the screening was performed through the analysis of titles and/or abstracts. The criteria were: including clinical studies in general, randomized or not, in the period of 10 years prior to the research, in the English literature; excluded: experimental studies, case reports, research in the development phase. Results: In the preliminary results, a total of studies (n=183) were found, (n=57) excluded, such as studies of cancer, diabetes, obesity, and skin diseases. Conclusion: To date, it has been identified that thyroid diseases can impair the fetus’s brain development. Further research is suggested on this matter to identify new substances that may have a potential therapeutic effect to aid the gestational period with thyroid diseases.

Keywords: pregnancy, thyroid, melatonin, high-risk pregnancy

Procedia PDF Downloads 107

Authors: Suman Som, Abhijit Maity, Sunil B. Daschakraborty, Sujit Chaudhuri, Manik Pradhan

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Background: Helicobacter pylori is a common and important human pathogen and the primary cause of peptic ulcer disease and gastric cancer. Currently H. pylori infection is detected by both invasive and non-invasive way but the diagnostic accuracy is not up to the mark. Aim: To set up an optimal diagnostic cut-off value of 13C-Urea Breath Test to detect H. pylori infection and evaluate a novel c-PDR methodology to overcome of inconclusive grey zone. Materials and Methods: All 83 subjects first underwent upper-gastrointestinal endoscopy followed by rapid urease test and histopathology and depending on these results; we classified 49 subjects as H. pylori positive and 34 negative. After an overnight, fast patients are taken 4 gm of citric acid in 200 ml water solution and 10 minute after ingestion of the test meal, a baseline exhaled breath sample was collected. Thereafter an oral dose of 75 mg 13C-Urea dissolved in 50 ml water was given and breath samples were collected upto 90 minute for 15 minute intervals and analysed by laser based high precisional cavity enhanced spectroscopy. Results: We studied the excretion kinetics of 13C isotope enrichment (expressed as δDOB13C ‰) of exhaled breath samples and found maximum enrichment around 30 minute of H. pylori positive patients, it is due to the acid mediated stimulated urease enzyme activity and maximum acidification happened within 30 minute but no such significant isotopic enrichment observed for H. pylori negative individuals. Using Receiver Operating Characteristic (ROC) curve an optimal diagnostic cut-off value, δDOB13C ‰ = 3.14 was determined at 30 minute exhibiting 89.16% accuracy. Now to overcome grey zone problem we explore percentage dose of 13C recovered per hour, i.e. 13C-PDR (%/hr) and cumulative percentage dose of 13C recovered, i.e. c-PDR (%) in exhaled breath samples for the present 13C-UBT. We further explored the diagnostic accuracy of 13C-UBT by constructing ROC curve using c-PDR (%) values and an optimal cut-off value was estimated to be c-PDR = 1.47 (%) at 60 minute, exhibiting 100 % diagnostic sensitivity , 100 % specificity and 100 % accuracy of 13C-UBT for detection of H. pylori infection. We also elucidate the gastric emptying process of present 13C-UBT for H. pylori positive patients. The maximal emptying rate found at 36 minute and half empting time of present 13C-UBT was found at 45 minute. Conclusions: The present study exhibiting the importance of c-PDR methodology to overcome of grey zone problem in 13C-UBT for accurate determination of infection without any risk of diagnostic errors and making it sufficiently robust and novel method for an accurate and fast non-invasive diagnosis of H. pylori infection for large scale screening purposes.

Keywords: 13C-Urea breath test, c-PDR methodology, grey zone, Helicobacter pylori

Procedia PDF Downloads 280

Authors: Akram Abi, Mohammad Hossein Sarrafzadeh

Abstract:

Because of their several advantages over chemical surfactants, biosurfactants have given rise to a growing interest in the past decades. Advantages such as lower toxicity, higher biodegradability, higher selectivity and applicable at extreme temperature and pH which enables them to be used in a variety of applications such as: enhanced oil recovery, environmental and pharmaceutical applications, etc. Bacillus subtilis produces a cyclic lipopeptide, called surfactin, which is one of the most powerful biosurfactants with ability to decrease surface tension of water from 72 mN/m to 27 mN/m. In addition to its biosurfactant character, surfactin exhibits interesting biological activities such as: inhibition of fibrin clot formation, lyses of erythrocytes and several bacterial spheroplasts, antiviral, anti-tumoral and antibacterial properties. Surfactin is an antibiotic substance and has been shown recently to possess anti-HIV activity. However, application of biosurfactants is limited by their high production cost. The cost can be reduced by optimizing biosurfactant production using cheap feed stock. Utilization of inexpensive substrates and unconventional carbon sources like urban or agro-industrial wastes is a promising strategy to decrease the production cost of biosurfactants. With suitable engineering optimization and microbiological modifications, these wastes can be used as substrates for large-scale production of biosurfactants. As an effort to fulfill this purpose, in this work we have tried to utilize olive oil as second carbon source and also yeast extract as second nitrogen source to investigate the effect on both biomass and biosurfactant production improvement in Bacillus subtilis cultures. Since the turbidity of the culture was affected by presence of the oil, optical density was compromised and no longer could be used as an index of growth and biomass concentration. Therefore, cell Dry Weight measurements with applying necessary tactics for removing oil drops to prevent interference with biomass weight were carried out to monitor biomass concentration during the growth of the bacterium. The surface tension and critical micelle dilutions (CMD-1, CMD-2) were considered as an indirect measurement of biosurfactant production. Distinctive and promising results were obtained in the cultures containing olive oil compared to cultures without it: more than two fold increase in biomass production (from 2 g/l to 5 g/l) and considerable reduction in surface tension, down to 40 mN/m at surprisingly early hours of culture time (only 5hr after inoculation). This early onset of biosurfactant production in this culture is specially interesting when compared to the conventional cultures at which this reduction in surface tension is not obtained until 30 hour of culture time. Reducing the production time is a very prominent result to be considered for large scale process development. Furthermore, these results can be used to develop strategies for utilization of agro-industrial wastes (such as olive oil mill residue, molasses, etc.) as cheap and easily accessible feed stocks to decrease the high costs of biosurfactant production.

Keywords: agro-industrial waste, bacillus subtilis, biosurfactant, fermentation, second carbon and nitrogen source, surfactin

Procedia PDF Downloads 268

Authors: Alan N. A. Heberle, Salatiel W. Da Silva, Valentin Perez-Herranz, Andrea M. Bernardes

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Contaminants of emerging concern are substances widely used, such as pharmaceutical products. These compounds represent risk for both wild and human life since they are not completely removed from wastewater by conventional wastewater treatment plants. In the environment, they can be harm even in low concentration (µ or ng/L), causing bacterial resistance, endocrine disruption, cancer, among other harmful effects. One of the most common taken medicine to treat cardiocirculatory diseases is the Atenolol (ATL), a β-Blocker, which is toxic to aquatic life. In this way, it is necessary to implement a methodology, which is capable to promote the degradation of the ATL, to avoid the environmental detriment. A very promising technology is the advanced electrochemical oxidation (AEO), which mechanisms are based on the electrogeneration of reactive radicals (mediated oxidation) and/or on the direct substance discharge by electron transfer from contaminant to electrode surface (direct oxidation). The hydroxyl (HO•) and sulfate (SO₄•⁻) radicals can be generated, depending on the reactional medium. Besides that, at some condition, the peroxydisulfate (S₂O₈²⁻) ion is also generated from the SO₄• reaction in pairs. Both radicals, ion, and the direct contaminant discharge can break down the molecule, resulting in the degradation and/or mineralization. However, ATL molecule and byproducts can still remain in the treated solution. On this wise, some efforts can be done to implement the AEO process, being one of them the use of a cationic membrane to separate the cathodic (reduction) from the anodic (oxidation) reactor compartment. The aim of this study is investigate the influence of the implementation of a cationic membrane (Nafion®-117) to separate both cathodic and anodic, AEO reactor compartments. The studied reactor was a filter-press, with bath recirculation mode, flow 60 L/h. The anode was an Nb/BDD2500 and the cathode a stainless steel, both bidimensional, geometric surface area 100 cm². The solution feeding the anodic compartment was prepared with ATL 100 mg/L using Na₂SO₄ 4 g/L as support electrolyte. In the cathodic compartment, it was used a solution containing Na₂SO₄ 71 g/L. Between both solutions was placed the membrane. The applied currents densities (iₐₚₚ) of 5, 20 and 40 mA/cm² were studied over 240 minutes treatment time. Besides that, the ATL decay was analyzed by ultraviolet spectroscopy (UV/Vis). The mineralization was determined performing total organic carbon (TOC) in TOC-L CPH Shimadzu. In the cases without membrane, the iₐₚₚ 5, 20 and 40 mA/cm² resulted in 55, 87 and 98 % ATL degradation at the end of treatment time, respectively. However, with membrane, the degradation, for the same iₐₚₚ, was 90, 100 and 100 %, spending 240, 120, 40 min for the maximum degradation, respectively. The mineralization, without membrane, for the same studied iₐₚₚ, was 40, 55 and 72 %, respectively at 240 min, but with membrane, all tested iₐₚₚ reached 80 % of mineralization, differing only in the time spent, 240, 150 and 120 min, for the maximum mineralization, respectively. The membrane increased the ATL oxidation, probably due to avoid oxidant ions (S₂O₈²⁻) reduction on the cathode surface.

Keywords: contaminants of emerging concern, advanced electrochemical oxidation, atenolol, cationic membrane, double compartment reactor

Procedia PDF Downloads 110

Authors: María José Carrero, Ana M. Borreguero, Juan F. Rodríguez, María M. Velencoso, Ángel Serrano, María Jesús Ramos

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Flame-retardants are incorporated in different materials in order to reduce the risk of fire, either by providing increased resistance to ignition, or by acting to slow down combustion and thereby delay the spread of flames. In this work, polyether polyols with fire retardant properties were synthesized due to their wide application in the polyurethanes formulation. The combustion of polyurethanes is primarily dependent on the thermal properties of the polymer, the presence of impurities and formulation residue in the polymer as well as the supply of oxygen. There are many types of flame retardants, most of them are phosphorous compounds of different nature and functionality. The addition of these compounds is the most common method for the incorporation of flame retardant properties. The employment of glycerol phosphate sodium salt as initiator for the polyol synthesis allows obtaining polyols with phosphate groups in their structure. However, some of the critical points of the use of glycerol phosphate salt are: the lower reactivity of the salt and the necessity of a solvent (dimethyl sulfoxide, DMSO). Thus, the main aim in the present work was to determine the amount of the solvent needed to get a good solubility of the initiator salt. Although the anionic polymerization mechanism of polyether formation is well known, it seems convenient to clarify the role that DMSO plays at the starting point of the polymerization process. Regarding the fact that the catalyst deprotonizes the hydroxyl groups of the initiator and as a result of this, two water molecules and glycerol phosphate alkoxide are formed. This alkoxide, together with DMSO, has to form a homogeneous mixture where the initiator (solid) and the propylene oxide (PO) are soluble enough to mutually interact. The addition rate of PO increased when the solvent/initiator ratios studied were increased, observing that it also made the initiation step shorter. Furthermore, the molecular weight of the polyol decreased when higher solvent/initiator ratios were used, what revealed that more amount of salt was activated, initiating more chains of lower length but allowing to react more phosphate molecules and to increase the percentage of phosphorous in the final polyol. However, the final phosphorous content was lower than the theoretical one because only a percentage of salt was activated. On the other hand, glycerol phosphate disodium salt was still partially insoluble in DMSO studied proportions, thus, the recovery and reuse of this part of the salt for the synthesis of new flame retardant polyols was evaluated. In the recovered salt case, the rate of addition of PO remained the same than in the commercial salt but a shorter induction period was observed, this is because the recovered salt presents a higher amount of deprotonated hydroxyl groups. Besides, according to molecular weight, polydispersity index, FT-IR spectrum and thermal stability, there were no differences between both synthesized polyols. Thus, it is possible to use the recovered glycerol phosphate disodium salt in the same way that the commercial one.

Keywords: DMSO, fire retardants, glycerol phosphate disodium salt, recovered initiator, solvent

Procedia PDF Downloads 250

Authors: Lena Lapidot, Amir Amnon, Rita Nosenko, Veitsman Ella, Cohen-Ezra Oranit, Davidov Yana, Segev Shlomo, Koren Omry, Safran Michal, Ben-Ari Ziv

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Introduction: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related mortality worldwide. Liver Cirrhosis is the main predisposing risk factor for the development of HCC. The factor(s) influencing disease progression from Cirrhosis to HCC remain unknown. Gut microbiota has recently emerged as a major player in different liver diseases, however its association with HCC is still a mystery. Moreover, there might be an important association between the gut microbiota, nutrition, life style and the progression of Cirrhosis and HCC. The aim of our study was to characterize the gut microbial signature in association with life style and nutrition of patients with Cirrhosis, HCC-Cirrhosis and healthy controls. Design: Stool samples were collected from 95 individuals (30 patients with HCC, 38 patients with Cirrhosis and 27 age, gender and BMI-matched healthy volunteers). All participants answered lifestyle and Food Frequency Questionnaires. 16S rRNA sequencing of fecal DNA was performed (MiSeq Illumina). Results: There was a significant decrease in alpha diversity in patients with Cirrhosis (qvalue=0.033) and in patients with HCC-Cirrhosis (qvalue=0.032) compared to healthy controls. The microbiota of patients with HCC-cirrhosis compared to patients with Cirrhosis, was characterized by a significant overrepresentation of Clostridium (pvalue=0.024) and CF231 (pvalue=0.010) and lower expression of Alphaproteobacteria (pvalue=0.039) and Verrucomicrobia (pvalue=0.036) in several taxonomic levels: Verrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae and the genus Akkermansia (pvalue=0.039). Furthermore, we performed an analysis of predicted metabolic pathways (Kegg level 2) that resulted in a significant decrease in the diversity of metabolic pathways in patients with HCC-Cirrhosis (qvalue=0.015) compared to controls, one of which was amino acid metabolism. Furthermore, investigating the life style and nutrition habits of patients with HCC-Cirrhosis, we found significant correlations between intake of artificial sweeteners and Verrucomicrobia (qvalue=0.12), High sugar intake and Synergistetes (qvalue=0.021) and High BMI and the pathogen Campylobacter (qvalue=0.066). Furthermore, overweight in patients with HCC-Cirrhosis modified bacterial diversity (qvalue=0.023) and composition (qvalue=0.033). Conclusions: To the best of the our knowledge, we present the first report of the gut microbial composition in patients with HCC-Cirrhosis, compared with Cirrhotic patients and healthy controls. We have demonstrated in our study that there are significant differences in the gut microbiome of patients with HCC-cirrhosis compared to Cirrhotic patients and healthy controls. Our findings are even more pronounced because the significantly increased bacteria Clostridium and CF231 in HCC-Cirrhosis weren't influenced by diet and lifestyle, implying this change is due to the development of HCC. Further studies are needed to confirm these findings and assess causality.

Keywords: Cirrhosis, Hepatocellular carcinoma, life style, liver disease, microbiome, nutrition

Procedia PDF Downloads 95

Authors: S. B. Q. Tran

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Drop condensation is the phenomenon that the tiny drops form when the oversaturated vapour present in the environment condenses on a substrate and makes the droplet growth. Recently, this subject has received much attention due to its applications in many fields such as thin film growth, heat transfer, recovery of atmospheric water and polymer templating. In literature, many papers investigated theoretically and experimentally in macro droplet growth with the size of millimeter scale of radius. However few papers about nanodroplet condensation are found in the literature especially theoretical work. In order to understand the droplet growth in nanoscale, we perform the numerical simulation work to study nanodroplet growth. We investigate and discuss the role of the droplet shape and monomer diffusion on drop growth and their effect on growth law. The effect of droplet shape is studied by doing parametric studies of contact angle and disjoining pressure magnitude. Besides, the effect of pinning and de-pinning behaviours is also studied. We investigate the axisymmetric homogeneous growth of 10–100 nm single water nanodroplet on a substrate surface. The main mechanism of droplet growth is attributed to the accumulation of laterally diffusing water monomers, formed by the absorption of water vapour in the environment onto the substrate. Under assumptions of quasi-steady thermodynamic equilibrium, the nanodroplet evolves according to the augmented Young–Laplace equation. Using continuum theory, we model the dynamics of nanodroplet growth including the coupled effects of disjoining pressure, contact angle and monomer diffusion with the assumption of constant flux of water monomers at the far field. The simulation result is validated by comparing with the published experimental result. For the case of nanodroplet growth with constant contact angle, our numerical results show that the initial droplet growth is transient by monomer diffusion. When the flux at the far field is small, at the beginning, the droplet grows by the diffusion of initially available water monomers on the substrate and after that by the flux at the far field. In the steady late growth rate of droplet radius and droplet height follow a power law of 1/3, which is unaffected by the substrate disjoining pressure and contact angle. However, it is found that the droplet grows faster in radial direction than high direction when disjoining pressure and contact angle increase. The simulation also shows the information of computational domain effect in the transient growth period. When the computational domain size is larger, the mass coming in the free substrate domain is higher. So the mass coming in the droplet is also higher. The droplet grows and reaches the steady state faster. For the case of pinning and de-pinning droplet growth, the simulation shows that the disjoining pressure does not affect the droplet radius growth law 1/3 in steady state. However the disjoining pressure modifies the growth rate of the droplet height, which then follows a power law of 1/4. We demonstrate how spatial depletion of monomers could lead to a growth arrest of the nanodroplet, as observed experimentally.

Keywords: augmented young-laplace equation, contact angle, disjoining pressure, nanodroplet growth

Procedia PDF Downloads 245

Authors: Mateusz Bilski, Jakub Klas, Emilia Kowalczyk, Sylwia Koziej, Katarzyna Kulszo, Ludmiła Grzybowska- Szatkowska

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Background: Liver metastases are a common complication of primary solid tumors and sig-nificantly reduce patient survival. In the era of increasing diagnosis of oligometastatic disease and oligoprogression, methods of local treatment of metastases, i.e. MDT, are becoming more important. Implementation of such treatment can be considered for liver metastases, which are a common complication of primary solid tumors and significantly reduce patient survival. To date, the mainstay of treatment for oligometastatic disease has been surgical resection, but not all patients qualify for the procedure. As an alternative to surgical resection, radiotherapy techniques have become available, including stereotactic body radiation therapy (SBRT) or high-dose interstitial brachytherapy (iBT). iBT is an invasive method that emits very high doses of radiation from the inside of the tumor to the outside. This technique provides better tumor coverage than SBRT while having little impact on surrounding healthy tissue and elim-inates some concerns involving respiratory motion. Methods: We conducted a systematic re-view of the scientific literature on the use of brachytherapy in the treatment of liver metasta-ses from 2018 - 2023 using PubMed and ResearchGate browsers according to PRISMA rules. Results: From 111 articles, 18 publications containing information on 729 patients with liver metastases were selected. iBT has been shown to provide high rates of tumor control. Among 14 patients with 54 unresectable RCC liver metastases, after iBT LTC was 92.6% during a median follow-up of 10.2 months, PFS was 3.4 months. In analysis of 167 patients after treatment with a single fractional dose of 15-25 Gy with brachytherapy at 6- and 12-month follow-up, LRFS rates of 88,4-88.7% and 70.7 - 71,5%, PFS of 78.1 and 53.8%, and OS of 92.3 - 96.7% and 76,3% - 79.6%, respectively, were achieved. No serious complications were observed in all patients. Distant intrahepatic progression occurred later in patients with unre-sectable liver metastases after brachytherapy (PFS: 19.80 months) than in HCC patients (PFS: 13.50 months). A significant difference in LRFS between CRC patients (84.1% vs. 50.6%) and other histologies (92.4% vs. 92.4%) was noted, suggesting a higher treatment dose is necessary for CRC patients. The average target dose for metastatic colorectal cancer was 40 - 60 Gy (compared to 100 - 250 Gy for HCC). To better assess sensitivity to therapy and pre-dict side effects, it has been suggested that humoral mediators be evaluated. It was also shown that baseline levels of TNF-α, MCP-1 and VEGF, as well as NGF and CX3CL corre-lated with both tumor volume and radiation-induced liver damage, one of the most serious complications of iBT, indicating their potential role as biomarkers of therapy outcome. Con-clusions: The use of brachytherapy methods in the treatment of liver metastases of various cancers appears to be an interesting and relatively safe therapeutic method alternative to sur-gery. An important challenge remains the selection of an appropriate brachytherapy method and radiation dose for the corresponding initial tumor type from which the metastasis origi-nated.

Keywords: liver metastases, brachytherapy, CT-HDRBT, iBT

Procedia PDF Downloads 84

Authors: Rajkumar Ghosh

Abstract:

The industrialization of coal mining and related activities has a significant impact on groundwater in the surrounding areas of the Damodar River. The Damodar River basin, located in eastern India, is known as the "Ruhr of India" due to its abundant coal reserves and extensive coal mining and industrial operations. One of the major consequences of collieries on groundwater is the contamination of water sources. Coal mining activities often involve the excavation and extraction of coal through underground or open-pit mining methods. These processes can release various pollutants and chemicals into the groundwater, including heavy metals, acid mine drainage, and other toxic substances. As a result, the quality of groundwater in the Damodar River region has deteriorated, making it unsuitable for drinking, irrigation, and other purposes. The high concentration of heavy metals, such as arsenic, lead, and mercury, in the groundwater has posed severe health risks to the local population. Prolonged exposure to contaminated water can lead to various health problems, including skin diseases, respiratory issues, and even long-term ailments like cancer. The contamination has also affected the aquatic ecosystem, harming fish populations and other organisms dependent on the river's water. Moreover, the excessive extraction of groundwater for industrial processes, including coal washing and cooling systems, has resulted in a decline in the water table and depletion of aquifers. This has led to water scarcity and reduced availability of water for agricultural activities, impacting the livelihoods of farmers in the region. Efforts have been made to mitigate these issues through the implementation of regulations and improved industrial practices. However, the historical legacy of coal industrialization continues to impact the groundwater in the Damodar River area. Remediation measures, such as the installation of water treatment plants and the promotion of sustainable mining practices, are essential to restore the quality of groundwater and ensure the well-being of the affected communities. In conclusion, the coal industrialization in the Damodar River surrounding has had a detrimental impact on groundwater. This research focuses on soil subsidence induced by the over-exploitation of ground water for dewatering open pit coal mines. Soil degradation happens in arid and semi-arid regions as a result of land subsidence in coal mining region, which reduces soil fertility. Depletion of aquifers, contamination, and water scarcity are some of the key challenges resulting from these activities. It is crucial to prioritize sustainable mining practices, environmental conservation, and the provision of clean drinking water to mitigate the long-lasting effects of collieries on the groundwater resources in the region.

Keywords: coal mining, groundwater, soil subsidence, water table, damodar river

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Authors: Simona Perga, Chiara Beltramo, Floriana Fruscione, Isabella Martini, Federica Cavallo, Federica Riccardo, Paolo Buracco, Selina Iussich, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari, Paola Modesto

Abstract:

Introduction: Human and canine melanoma have common clinical, histologic characteristics making dogs a good model for comparative oncology. The identification of specific genes and a better understanding of the genetic landscape, signaling pathways, and tumor–microenvironmental interactions involved in the cancer onset and progression is essential for the development of therapeutic strategies against this tumor in both species. In the present study, the differential expression of genes in spontaneously occurring canine melanoma and in paired normal tissue was investigated by targeted RNAseq. Material and Methods: Total RNA was extracted from 17 canine malignant melanoma (CMM) samples and from five paired normal tissues stored in RNA-later. In order to capture the greater genetic variability, gene expression analysis was carried out using two panels (Qiagen): Human Immuno-Oncology (HIO) and Mouse-Immuno-Oncology (MIO) and the miSeq platform (Illumina). These kits allow the detection of the expression profile of 990 genes involved in the immune response against tumors in humans and mice. The data were analyzed through the CLCbio Genomics Workbench (Qiagen) software using the Canis lupus familiaris genome as a reference. Data analysis were carried out both comparing the biologic group (tumoral vs. healthy tissues) and comparing neoplastic tissue vs. paired healthy tissue; a Fold Change greater than two and a p-value less than 0.05 were set as the threshold to select interesting genes. Results and Discussion: Using HIO 63, down-regulated genes were detected; 13 of those were also down-regulated comparing neoplastic sample vs. paired healthy tissue. Eighteen genes were up-regulated, 14 of those were also down-regulated comparing neoplastic sample vs. paired healthy tissue. Using the MIO, 35 down regulated-genes were detected; only four of these were down-regulated, also comparing neoplastic sample vs. paired healthy tissue. Twelve genes were up-regulated in both types of analysis. Considering the two kits, the greatest variation in Fold Change was in up-regulated genes. Dogs displayed a greater genetic homology with humans than mice; moreover, the results have shown that the two kits are able to detect different genes. Most of these genes have specific cellular functions or belong to some enzymatic categories; some have already been described to be correlated to human melanoma and confirm the validity of the dog as a model for the study of molecular aspects of human melanoma.

Keywords: animal model, canine melanoma, gene expression, spontaneous tumors, targeted RNAseq

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Authors: Ashima Sharma

Abstract:

Human Serum Albumin (HSA)- one of the most demanded therapeutic proteins with immense biotechnological applications- is a large multidomain protein containing 17 disulfide bonds. The current source of HSA is human blood plasma which is a limited and unsafe source. Thus, there exists an indispensable need to promote non-animal derived recombinant HSA (rHSA) production. Escherichia coli is one of the most convenient hosts which had contributed to the production of more than 30% of the FDA approved recombinant pharmaceuticals. It grows rapidly and reaches high cell density using inexpensive and simple substrates. E. coli derived recombinant products have more economic potential as fermentation processes are cheaper compared to the other expression hosts. The major bottleneck in exploiting E. coli as a host for a disulfide-rich multidomain protein is the formation of aggregates of overexpressed protein. The majority of the expressed HSA forms inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA from inclusion bodies is not preferred because it is difficult to obtain a large multidomain disulfide bond rich protein like rHSA in its functional native form. Purification is tedious, time-consuming, laborious and expensive. Because of such limitations, the E. coli host system was neglected for rHSA production for the past few decades despite its numerous advantages. In the present work, we have exploited the capabilities of E. coli as a host for the enhanced functional production of rHSA (~60% of the total expressed rHSA in the soluble fraction). Parameters like intracellular environment, temperature, induction type, duration of induction, cell lysis conditions etc. which play an important role in enhancing the level of production of the desired protein in its native form in vivo have been optimized. We have studied the effect of assistance of different types of exogenously employed chaperone systems on the functional expression of rHSA in the E. coli host system. Different aspects of cell growth parameters during the production of rHSA in presence and absence of molecular chaperones in E. coli have also been studied. Upon overcoming the difficulties to produce functional rHSA in E. coli, it has been possible to produce significant levels of functional protein through engineering the biological system of protein folding in the cell, the E. coli-derived rHSA has been purified to homogeneity. Its detailed physicochemical characterization has been performed by monitoring its conformational properties, secondary and tertiary structure elements, surface properties, ligand binding properties, stability issues etc. These parameters of the recombinant protein have been compared with the naturally occurring protein from the human source. The outcome of the comparison reveals that the recombinant protein resembles exactly the same as the natural one. Hence, we propose that the E. coli-derived rHSA is an ideal biosimilar for human blood plasma-derived serum albumin. Therefore, in the present study, we have introduced and promoted the E. coli- derived rHSA as an alternative to the preparation from a human source, pHSA.

Keywords: recombinant human serum albumin, Escherichia coli, biosimilar, chaperone assisted protein folding

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Authors: Catarina Bento, Ana Carolina Gonçalves, Fábio Jesus, Luís Rodrigues Silva

Abstract:

Increasing evidence suggests that a diet rich in fruits and vegetables plays important roles in the prevention of chronic diseases, such as heart disease, cancer, stroke, diabetes, Alzheimer’s disease, among others. Fruits and vegetables gained prominence due their richness in bioactive compounds, being the focus of many studies due to their biological properties acting as health promoters. Prunus avium Linnaeus (L.), commonly known as sweet cherry has been the centre of attention due to its health benefits, and has been highly studied. In Portugal, most of the cherry production comes from the Fundão region. The Saco is one of the most important cultivar produced in this region, attributed with geographical protection. In this work, we prepared 3 extracts through solid-phase extraction (SPE): a whole extract, fraction I (non-coloured phenolics) and fraction II (coloured phenolics). The three extracts were used to determine the phenolic profile of Saco cultivar by liquid chromatography with diode array detection (LC-DAD) technique. This was followed by the evaluation of their biological potential, testing the extracts’ capacity to scavenge free-radicals (DPPH•, nitric oxide (•NO) and superoxide radical (O2●-)) and to inhibit α-glucosidase enzyme of all extracts. Additionally, we evaluated, for the first time, the protective effects against peroxyl radical (ROO•)-induced hemoglobin oxidation and hemolysis in human erythrocytes. A total of 16 non-coloured phenolics were detected, 3-O-caffeoylquinic and ρ-coumaroylquinic acids were the main ones, and 6 anthocyanins were found, among which cyanidin-3-O-rutinoside represented the majority. In respect to antioxidant activity, Saco showed great antioxidant potential in a concentration-dependent manner, demonstrated through the DPPH•,•NO and O2●-radicals, and greater ability to inhibit the α-glucosidase enzyme in comparison to the regular drug acarbose used to treat diabetes. Additionally, Saco proved to be effective to protect erythrocytes against oxidative damage in a concentration-dependent manner against hemoglobin oxidation and hemolysis. Our work demonstrated that Saco cultivar is an excellent source of phenolic compounds which are natural antioxidants that easily capture reactive species, such as ROO• before they can attack the erythrocytes’ membrane. In a general way, the whole extract showed the best efficiency, most likely due to a synergetic interaction between the different compounds. Finally, comparing the two separate fractions, the coloured fraction showed the most activity in all the assays, proving to be the biggest contributor of Saco cherries’ biological activity.

Keywords: biological potential, coloured phenolics, non-coloured phenolics, sweet cherry

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Authors: Maritza Estela Garay-Rodriguez, Mirella Gutierrez-Arzaluz, Miguel Torres-Rodriguez, Violeta Mugica-Alvarez

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Arsenic is an element present in the earth's crust and is dispersed in the environment through natural processes and some anthropogenic activities. Naturally released into the environment through the weathering and erosion of sulphides mineral, some activities such as mining, the use of pesticides or wood preservatives potentially increase the concentration of arsenic in air, water, and soil. The natural arsenic release of a geological material is a threat to the world's drinking water sources. In aqueous phase is found in inorganic form, as arsenate and arsenite mainly, the contamination of groundwater by salts of this element originates what is known as endemic regional hydroarsenicism. The International Agency for Research on Cancer (IARC) categorizes the inorganic As within group I, as a substance with proven carcinogenic action for humans. It has been found the presence of As in groundwater in several countries such as Argentina, Mexico, Bangladesh, Canada and the United States. Regarding the concentration of arsenic in drinking water according to the World Health Organization (WHO) and the Environmental Protection Agency (EPA) establish maximum concentrations of 10 μg L⁻¹. In Mexico, in some states as Hidalgo, Morelos and Michoacán concentrations of arsenic have been found in bodies of water around 1000 μg L⁻¹, a concentration that is well above what is allowed by Mexican regulations with the NOM-127- SSA1-1994 that establishes a limit of 25 μg L⁻¹. Given this problem in Mexico, this research proposes the use of a natural Mexican zeolite (clinoptilolite type) native to the district of Etla in the central valley region of Oaxaca, as an adsorbent for the removal of arsenic. The zeolite was subjected to a conditioning with iron oxide by the precipitation-impregnation method with 0.5 M iron nitrate solution, in order to increase the natural adsorption capacity of this material. The removal of arsenic was carried out in a column with a fixed bed of conditioned zeolite, since it combines the advantages of a conventional filter with those of a natural adsorbent medium, providing a continuous treatment, of low cost and relatively easy to operate, for its implementation in marginalized areas. The zeolite was characterized by XRD, SEM/EDS, and FTIR before and after the arsenic adsorption tests, the results showed that the modification methods used are adequate to prepare adsorbent materials since it does not modify its structure, the results showed that with a particle size of 1.18 mm, an initial concentration of As (V) ions of 1 ppm, a pH of 7 and at room temperature, a removal of 98.7% was obtained with an adsorption capacity of 260 μg As g⁻¹ zeolite. The results obtained indicated that the conditioned zeolite is favorable for the elimination of arsenate in water containing up to 1000 μg As L⁻¹ and could be suitable for removing arsenate from pits of water.

Keywords: adsorption, arsenic, iron conditioning, natural zeolite

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Authors: Neha P. Amin, Maliha Zainib, Sean Parker, Malcolm Mattes

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Purpose/Objectives: Combination immunotherapy (IT) and radiation therapy (RT) is an actively growing field of clinical investigation due to promising findings of synergistic effects from immune-mediated mechanisms observed in preclinical studies and clinical data from case reports of abscopal effects. While there are many ongoing trials of combined IT-RT, there are still limited data on toxicity and outcome optimization regarding RT dose, fractionation, and sequencing of RT with IT. Nivolumab (NIVO), an anti-PD-1 monoclonal antibody, has been rapidly adopted in the clinic over the past 2 years, resulting in more patients being considered for concurrent RT-NIVO. Knowledge about the toxicity profile of combined RT-NIVO is important for both the patient and physician when making educated treatment decisions. The acute toxicity profile of concurrent RT-NIVO was analyzed in this study. Materials/Methods: A retrospective review of all consecutive patients who received NIVO from 1/2015 to 5/2017 at 4 separate centers within two separate institutions was performed. Those patients who completed a course of RT from 1 day prior to initial NIVO infusion through 1 month after last NIVO infusion were considered to have received concurrent therapy and included in the subsequent analysis. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed acute toxicities within 3 months of RT completion. Results: Among 261 patients who received NIVO, 46 (17.6%) received concurrent RT to 67 different sites. The median f/u was 3.3 (.1-19.8) months, and 11/46 (24%) were still alive at last analysis. The most common histology, RT prescription, and treatment site included non-small cell lung cancer (23/46, 50%), 30 Gy in 10 fractions (16/67, 24%), and central thorax/abdomen (26/67, 39%), respectively. 79% (53/67) of irradiated sites were treated with 3D-conformal technique and palliative dose-fractionation. Grade 3, 4, and 5 toxicities were experienced by 11, 1, and 2 patients, respectively. However all grade 4 and 5 toxicities were outside of the irradiated area and attributed to the NIVO alone, and only 4/11 (36%) of the grade 3 toxicities were attributed to the RT-NIVO. The irradiated site in these cases included the brain [2/10 (20%)] and central thorax/abdomen [2/19 (10.5%)], including one unexpected grade 3 pancreatitides following stereotactic body RT to the left adrenal gland. Conclusions: Concurrent RT-NIVO is generally well tolerated, though with potentially increased rates of severe toxicity when irradiating the lung, abdomen, or brain. Pending more definitive data, we recommend counseling patients on the potentially increased rates of side effects from combined immunotherapy and radiotherapy to these locations. Future prospective trials assessing fractionation and sequencing of RT with IT will help inform combined therapy recommendations.

Keywords: combined immunotherapy and radiation, immunotherapy, Nivolumab, toxicity of concurrent immunotherapy and radiation

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Authors: Chee Wai Ku, Pui See Chin

Abstract:

As an emerging alternative to hysterectomy, uterine artery embolization (UAE) has been widely used in the management of fibroids and in controlling postpartum hemorrhage (PPH) unresponsive to other therapies. Research has shown UAE to be a safe, minimally invasive procedure with few complications and minimal effects on future fertility. We present two cases highlighting the use of UAE in preventing PPH in a patient with a large fibroid at the time of cesarean section and in the treatment of secondary PPH refractory to other therapies in another patient. We present a 36-year primiparous woman who booked at 18+6 weeks gestation with a 13.7 cm subserosal fibroid at the lower anterior wall of the uterus near the cervix and a 10.8 cm subserosal fibroid in the left wall. Prophylactic internal iliac artery occlusion balloons were placed prior to the planned classical midline cesarean section. The balloons were inflated once the baby was delivered. Bilateral uterine arteries were embolized subsequently. The estimated blood loss (EBL) was 400 mls and hemoglobin (Hb) remained stable at 10 g/DL. Ultrasound scan 2 years postnatally showed stable uterine fibroids 10.4 and 7.1 cm, which was significantly smaller than before. We present the second case of a 40-year-old G2P1 with a previous cesarean section for failure to progress. There were no antenatal problems, and the placenta was not previa. She presented with term labour and underwent an emergency cesarean section for failed vaginal birth after cesarean. Intraoperatively extensive adhesions were noted with bladder drawn high, and EBL was 300 mls. Postpartum recovery was uneventful. She presented with secondary PPH 3 weeks later complicated by hypovolemic shock. She underwent an emergency examination under anesthesia and evacuation of the uterus, with EBL 2500mls. Histology showed decidua with chronic inflammation. She was discharged well with no further PPH. She subsequently returned one week later for secondary PPH. Bedside ultrasound showed that the endometrium was thin with no evidence of retained products of conception. Uterotonics were administered, and examination under anesthesia was performed, with uterine Bakri balloon and vaginal pack insertion after. EBL was 1000 mls. There was no definite cause of PPH with no uterine atony or products of conception. To evaluate a potential cause, pelvic angiogram and super selective left uterine arteriogram was performed which showed profuse contrast extravasation and acute bleeding from the left uterine artery. Superselective embolization of the left uterine artery was performed. No gross contrast extravasation from the right uterine artery was seen. These two cases demonstrated the superior efficacy of UAE. Firstly, the prophylactic use of intra-arterial balloon catheters in pregnant patients with large fibroids, and secondly, in the diagnosis and management of secondary PPH refractory to uterotonics and uterine tamponade. In both cases, the need for laparotomy hysterectomy was avoided, resulting in the preservation of future fertility. UAE should be a consideration for hemodynamically stable patients in centres with access to interventional radiology.

Keywords: fertility preservation, secondary postpartum hemorrhage, uterine embolization, uterine fibroids

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