Search results for: diseases
247 The Association of Vitamin B12 with Body Weight-and Fat-Based Indices in Childhood Obesity
Authors: Mustafa Metin Donma, Orkide Donma
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Vitamin deficiencies are common in obese individuals. Particularly, the status of vitamin B12 and its association with vitamin B9 (folate) and vitamin D is under investigation in recent time. Vitamin B12 is closely related to many vital processes in the body. In clinical studies, its involvement in fat metabolism draws attention from the obesity point of view. Obesity, in its advanced stages and in combination with metabolic syndrome (MetS) findings, may be a life-threatening health problem. Pediatric obesity is particularly important because it may be a predictor of severe chronic diseases during the adulthood period of the child. Due to its role in fat metabolism, vitamin B12 deficiency may disrupt metabolic pathways of the lipid and energy metabolisms in the body. The association of low B12 levels with obesity degree may be an interesting topic to be investigated. Obesity indices may be helpful at this point. Weight- and fat-based indices are available. Of them, body mass index (BMI) is in the first group. Fat mass index (FMI), fat-free mass index (FFMI) and diagnostic obesity notation model assessment-II (D2I) index lie in the latter group. The aim of this study is to clarify possible associations between vitamin B12 status and obesity indices in the pediatric population. The study comprises a total of one hundred and twenty-two children. Thirty-two children were included in the normal body mass index (N-BMI) group. Forty-six and forty-four children constitute groups with morbid obese children without MetS and with MetS, respectively. Informed consent forms and the approval of the institutional ethics committee were obtained. Tables prepared for obesity classification by World Health Organization were used. Metabolic syndrome criteria were defined. Anthropometric and blood pressure measurements were taken. Body mass index, FMI, FFMI, D2I were calculated. Routine laboratory tests were performed. Vitamin B9, B12, D concentrations were determined. Statistical evaluation of the study data was performed. Vitamin B9 and vitamin D levels were reduced in MetS group compared to children with N-BMI (p>0.05). Significantly lower values were observed in vitamin B12 concentrations of MetS group (p<0.01). Upon evaluation of blood pressure as well as triglyceride levels, there exist significant increases in morbid obese children. Significantly decreased concentrations of high density lipoprotein cholesterol were observed. All of the obesity indices and insulin resistance index exhibit increasing tendency with the severity of obesity. Inverse correlations were calculated between vitamin D and insulin resistance index as well as vitamin B12 and D2I in morbid obese groups. In conclusion, a fat-based index, D2I, was the most prominent body index, which shows a strong correlation with vitamin B12 concentrations in the late stage of obesity in children. A negative correlation between these two parameters was a confirmative finding related to the association between vitamin B12 and obesity degree.Keywords: body mass index, children, D2I index, fat mass index, obesity
Procedia PDF Downloads 206246 The Mitigation of Quercetin on Lead-Induced Neuroinflammation in a Rat Model: Changes in Neuroinflammatory Markers and Memory
Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi
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The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.Keywords: lead, quercetin, neuroinflammation, memory
Procedia PDF Downloads 53245 ‘Green Gait’ – The Growing Relevance of Podiatric Medicine amid Climate Change
Authors: Angela Evans, Gabriel Gijon-Nogueron, Alfonso Martinez-Nova
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Background The health sector, whose mission is protecting health, also contributes to the climate crisis, the greatest health threat of the 21st century. The carbon footprint from healthcare exceeds 5% of emissions globally, surpassing 7% in the USA and Australia. Global recognition has led to the Paris Agreement, the United Nations Sustainable Development Goals, and the World Health Organization's Climate Change Action Plan. It is agreed that the majority of health impacts stem from energy and resource consumption, as well as the production of greenhouse gases in the environment and deforestation. Many professional medical associations and healthcare providers advocate for their members to take the lead in environmental sustainability. Objectives To avail and expand ‘Green Podiatry’ via the three pillars of: Exercise ; Evidence ; Everyday changes; to highlight the benefits of physical activity and exercise for both human health and planet health. Walking and running are beneficial for health, provide low carbon transport, and have evidence-based health benefits. Podiatrists are key healthcare professionals in the physical activity space and can influence and guide their patients to increase physical activity and avert the many non-communicable diseases that are decimating public health, eg diabetes, arthritis, depression, cancer, obesity. Methods Publications, conference presentations, and pilot projects pertinent to ‘Green Podiatry’ have been activated since 2021, and a survey of podiatrist’s knowledge and awareness has been undertaken.The survey assessed attitudes towards environmental sustainability in work environment. The questions addressed commuting habits, hours of physical exercise per week, and attitudes in the clinic, such as prescribing unnecessary treatments or emphasizing sports as primary treatment. Results Teaching and Learning modules have been developed for podiatric medicine students and graduates globally. These will be availed. A pilot foot orthoses recycling project has been undertaken and will be reported, in addition to established footwear recycling. The preliminary survey found almost 90% of respondents had no knowledge of green podiatry or footwear recycling. Only 30% prescribe sports/exercise as the primary treatment for patients, and 45% do not to prescribe unnecessary treatments. Conclusions Podiatrists are in a good position to lead in the crucial area of healthcare and climate change implications. Sufficient education of podiatrists is essential for the profession to beneficially promote health and physical activity, which is beneficial for the health of all peoples and all communities.Keywords: climate change, gait, green, healthcare, sustainability
Procedia PDF Downloads 90244 Clinical Manifestations, Pathogenesis and Medical Treatment of Stroke Caused by Basic Mitochondrial Abnormalities (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes, MELAS)
Authors: Wu Liching
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Aim This case aims to discuss the pathogenesis, clinical manifestations and medical treatment of strokes caused by mitochondrial gene mutations. Methods Diagnosis of ischemic stroke caused by mitochondrial gene defect by means of "next-generation sequencing mitochondrial DNA gene variation detection", imaging examination, neurological examination, and medical history; this study took samples from the neurology ward of a medical center in northern Taiwan cases diagnosed with acute cerebral infarction as the research objects. Result This case is a 49-year-old married woman with a rare disease, mitochondrial gene mutation inducing ischemic stroke. She has severe hearing impairment and needs to use hearing aids, and has a history of diabetes. During the patient’s hospitalization, the blood test showed that serum Lactate: 7.72 mmol/L, Lactate (CSF) 5.9 mmol/L. Through the collection of relevant medical history, neurological evaluation showed changes in consciousness and cognition, slow response in language expression, and brain magnetic resonance imaging examination showed subacute bilateral temporal lobe infarction, which was an atypical type of stroke. The lineage DNA gene has m.3243A>G known pathogenic mutation point, and its heteroplasmic level is 24.6%. This pathogenic point is located in MITOMAP and recorded as Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) , Leigh Syndrome and other disease-related pathogenic loci, this mutation is located in ClinVar and recorded as Pathogenic (dbSNP: rs199474657), so it is diagnosed as a case of stroke caused by a rare disease mitochondrial gene mutation. After medical treatment, there was no more seizure during hospitalization. After interventional rehabilitation, the patient's limb weakness, poor language function, and cognitive impairment have all improved significantly. Conclusion Mitochondrial disorders can also be associated with abnormalities in psychological, neurological, cerebral cortical function, and autonomic functions, as well as problems with internal medical diseases. Therefore, the differential diagnoses cover a wide range and are not easy to be diagnosed. After neurological evaluation, medical history collection, imaging and rare disease serological examination, atypical ischemic stroke caused by rare mitochondrial gene mutation was diagnosed. We hope that through this case, the diagnosis of rare disease mitochondrial gene variation leading to cerebral infarction will be more familiar to clinical medical staff, and this case report may help to improve the clinical diagnosis and treatment for patients with similar clinical symptoms in the future.Keywords: acute stroke, MELAS, lactic acidosis, mitochondrial disorders
Procedia PDF Downloads 70243 Review of Published Articles on Climate Change and Health in Two Francophone Newspapers: 1990-2015
Authors: Mathieu Hemono, Sophie Puig-Malet, Patrick Zylberman, Avner Bar-Hen, Rainer Sauerborn, Stefanie Schütte, Niamh Herlihi, Antoine Flahault et Anneliese Depoux
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Since the IPCC released its first report in 1990, an increasing number of peer-reviewed publications have reported the health risks associated with climate change. Although there is a large body of evidence supporting the association between climate change and poor health outcomes, the media is inconsistent in the attention it pays to the subject matter. This study aims to analyze the modalities and rhetoric in the media concerning the impact of climate change on health in order to better understand its role in information dissemination. A review was conducted of articles published between 1990 and 2015 in the francophone newspapers Le Monde and Jeune Afrique. A detailed search strategy including specific climate and health terminology was used to search the newspapers’ online databases. 1202 articles were identified as having referenced the terms climate change and health. Inclusion and exclusion criteria were applied to narrow the search to articles referencing the effects of climate change on human health and 160 articles were included in the final analysis. Data was extracted and categorized to create a structured database allowing for further investigation and analysis. The review indicated that although 66% of the selected newspaper articles reference scientific evidence of the impact of climate change on human health, the focus on the topic is limited major political events or is circumstances relating to public health crises. Main findings also include that among the many direct and indirect health outcomes, infectious diseases are the main health outcome highlighted in association with climate change. Lastly, the articles suggest that while developed countries have caused most of the greenhouse effect, the global south is more immediately affected. Overall, the reviewed articles reinforce the need for international cooperation in finding a solution to mitigate the effects of climate change on health. The manner in which scientific results are communicated and disseminated, impact individual and collective perceptions of the topic in the public sphere and affect political will to shape policy. The results of this analysis will underline the modalities of the rhetoric of transparency and provide the basis for a perception study of media discourses. This study is part of an interdisciplinary project called 4CHealth that confronts results of the research done on scientific, political and press literature to better understand how the knowledge on climate changes and health circulates within those different fields and whether and how it is translated to real world change.Keywords: climate change, health, health impacts, communication, media, rhetoric, awareness, Global South, Africa
Procedia PDF Downloads 423242 Solid Waste and Its Impact on the Human Health
Authors: Waseem Akram, Hafiz Azhar Ali Khan
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Unplanned urbanization together with change in life from simple to more technologically advanced style with flow of rural masses to urban areas has played a vital role in pilling loads of solid wastes in our environment. The cities and towns have expanded beyond boundaries. Even the uncontrolled population expansion has caused the overall environmental burden. Thus, today the indifference remains as one of the biggest trash that has come up due to the non-responsive behavior of the people. Everyday huge amount of solid waste is thrown in the streets, on the roads, parks, and in all those places that are frequently and often visited by the human beings. This behavior based response in many countries of the world has led to serious health concerns and environmental issues. Over 80% of our products that are sold in the market are packed in plastic bags. None of the bags are later recycled but simply become a permanent environment concern that flies, choke lines or are burnt and release toxic gases in the environment or form dumps of heaps. Lack of classification of the daily waste generated from houses and other places lead to worst clogging of the sewerage lines and formation of ponding areas which ultimately favor vector borne disease and sometimes become a cause of transmission of polio virus. Solid waste heaps were checked at different places of the cities. All of the wastes on visual assessments were classified into plastic bags, papers, broken plastic pots, clay pots, steel boxes, wrappers etc. All solid waste dumping sites in the cities and wastes that were thrown outside of the trash containers usually contained wrappers, plastic bags, and unconsumed food products. Insect populations seen in these sites included the house flies, bugs, cockroaches and mosquito larvae breeding in water filled wrappers, containers or plastic bags. The population of the mosquitoes, cockroaches and houseflies were relatively very high in dumping sites close to human population. This population has been associated with cases like dengue, malaria, dysentery, gastro and also to skin allergies during the monsoon and summer season. Thus, dumping of the huge amount of solid wastes in and near the residential areas results into serious environmental concerns, bad smell circulation, and health related issues. In some places, the same waste is burnt to get rid of mosquitoes through smoke which ultimately releases toxic material in the atmosphere. Therefore, a proper environmental strategy is needed to minimize environmental burden and promote concepts of recycled products and thus, reduce the disease burden.Keywords: solid waste accumulation, disease burden, mosquitoes, vector borne diseases
Procedia PDF Downloads 278241 To Access the Knowledge, Awareness and Factors Associated With Diabetes Mellitus in Buea, Cameroon
Authors: Franck Acho
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This is a chronic metabolic disorder which is a fast-growing global problem with a huge social, health, and economic consequences. It is estimated that in 2010 there were globally 285 million people (approximately 6.4% of the adult population) suffering from this disease. This number is estimated to increase to 430 million in the absence of better control or cure. An ageing population and obesity are two main reasons for the increase. Diabetes mellitus is a chronic heterogeneous metabolic disorder with a complex pathogenesis. It is characterized by elevated blood glucose levels or hyperglycemia, which results from abnormalities in either insulin secretion or insulin action or both. Hyperglycemia manifests in various forms with a varied presentation and results in carbohydrate, fat, and protein metabolic dysfunctions. Long-term hyperglycemia often leads to various microvascular and macrovascular diabetic complications, which are mainly responsible for diabetes-associated morbidity and mortality. Hyperglycemia serves as the primary biomarker for the diagnosis of diabetes as well. Furthermore, it has been shown that almost 50% of the putative diabetics are not diagnosed until 10 years after onset of the disease, hence the real prevalence of global diabetes must be astronomically high. This study was conducted in a locality to access the level of knowledge, awareness and risk factors associated with people leaving with diabetes mellitus. A month before the screening was to be conducted, a health screening in some selected churches and on the local community radio as well as on relevant WhatsApp groups were advertised. A general health talk was delivered by the head of the screening unit to all attendees who were all educated on the procedure to be carried out with benefits and any possible discomforts after which the attendee’s consent was obtained. Evaluation of the participants for any leads to the diabetes selected for the screening was done by taking adequate history and physical examinations such as excessive thirst, increased urination, tiredness, hunger, unexplained weight loss, feeling irritable or having other mood changes, having blurry vision, having slow-healing sores, getting a lot of infections, such as gum, skin and vaginal infections. Out of the 94 participants the finding show that 78 were females and 16 were males, 70.21% of participants with diabetes were between the ages of 60-69yrs.The study found that only 10.63% of respondents declared a good level of knowledge of diabetes. Out of 3 symptoms of diabetes analyzed in this study, high blood sugar (58.5%) and chronic fatigue (36.17%) were the most recognized. Out of 4 diabetes risk factors analyzed in this study, obesity (21.27%) and unhealthy diet (60.63%) were the most recognized diabetes risk factors, while only 10.6% of respondents indicated tobacco use. The diabetic foot was the most recognized diabetes complication (50.57%), but some the participants indicated vision problems (30.8%),or cardiovascular diseases (20.21%) as diabetes complications.Keywords: diabetes mellitus, non comunicable disease, general health talk, hyperglycemia
Procedia PDF Downloads 56240 Midwives’ Perceptions and Experiences of Recommending and Delivering Vaccines to Pregnant Women Following the COVID-19 Pandemic
Authors: Cath Grimley, Debra Bick, Sarah Hillman, Louise Clarke, Helen Atherton, Jo Parsons
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The problem: Women in the UK are offered influenza (flu), pertussis (whooping cough) and COVID-19 vaccinations during their pregnancy but uptake of all three vaccines is below the desired rate. These vaccines are offered during pregnancy as pregnant women are at an increased risk of hospitalisation, morbidity, and mortality from these illnesses. Exposure to these diseases during pregnancy can also have a negative impact on the unborn baby with an increased risk of serious complications both while in utero and following birth. The research aims to explore perceptions about the vaccinations offered in pregnancy both from the perspectives of pregnant women and midwives. To determine factors that influence pregnant women’s decisions about whether or not to accept the vaccines following the Covid-19 pandemic and to explore midwives’ experiences of recommending and delivering vaccines. The approach: This research follows a qualitative design involving semi-structured interviews with pregnant women and midwives in the UK. Interviews with midwives explored vaccination discussions they routinely have with pregnant women and identified some of the barriers to vaccination that pregnant women discuss with them. Interviews with pregnant women explored their views since the COVID-19 pandemic about vaccinations offered during pregnancy, and whether the pandemic has influenced perceptions of vulnerability to illness in pregnant women. Midwives were recruited via participating hospitals and midwife specific social media groups. Pregnant women were recruited via participating hospitals and community groups. All interviews were conducted remotely (using telephone or Microsoft Teams) and analysed using thematic analysis. Findings: 43 pregnant women and 16 midwives were recruited and interviewed. The findings presented here will focus on data from midwives. Topics identified included three key themes for midwives. These were 1) Delivery of vaccinations which includes the convenience of offering vaccinations while attending standard antenatal appointments and practical barriers faced in delivering these vaccinations at hospital. 2) Messages and guidance included the importance of up-to-date informational needs for midwives to deliver vaccines and that uncertainty and conflicting messages about the COVID-19 vaccine during pregnancy were a barrier to delivery. 3) Recommendations to have vaccines look at all aspects of recommendations such as how recommendations are communicated, the contents of the recommendation, the importance of the vaccine and the impact of those recommendations on whether women accept the vaccine. Implications: Findings highlight the importance for midwives to receive clear and consistent information so they can feel confident in relaying this information while recommending and delivering vaccines to pregnant women. Emphasising why vaccines are important when recommending vaccinations to pregnant women in addition to standard information on the availability and timing will add to the strength and impact of that recommendation in helping women to make informed decisions about accepting vaccines. The findings of this study will inform the development of an intervention to increase vaccination uptake amongst pregnant women.Keywords: vaccination, pregnancy, qualitative, interviews, Covid-19, midwives
Procedia PDF Downloads 98239 Sumac Sprouts: From in Vitro Seed Germination to Chemical Characterization
Authors: Leto Leandra, Guaitini Caterina, Agosti Anna, Del Vecchio Lorenzo, Guarrasi Valeria, Cirlini Martina, Chiancone Benedetta
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To the best of our knowledge, this study represents the first attempt to investigate the in vitro germination response of Rhus coriaria L., and its sprout chemical characterization. Rhus coriaria L., a species belonging to the Anacardiaceae family, is commonly called "sumac" and is cultivated, in different countries of the Mediterranean and the Middle East regions, to produce a spice with a sour taste, obtained from its dried and ground fruits. Moreover, since ancient times, many beneficial properties have been attributed to this plant that has been used, in the traditional medicine of several Asian countries, against various diseases, including liver and intestinal pathologies, ulcers and various inflammatory states. In the recent past, sumac was cultivated in the Southern regions of Italy to treat leather, but its cultivation was abandoned, and currently, sumac plants grow spontaneously in marginal areas. Recently, in Italy, the interest in this species has been growing again, thanks to its numerous properties; thus, it becomes imperative to deepen the knowledge of this plant. In this study, in order to set up an efficient in vitro seed germination protocol, sumac seeds collected from spontaneous plants grown in Sicily, an island in the South of Italy, were, firstly, subjected to different treatments, scarification (mechanical, physical and chemical), cold stratification and imbibition, to break their physical and physiological dormancy, then, treated seeds were in vitro cultured on media with different gibberellic acid (GA3) concentrations. Results showed that, without any treatment, only 5% of in vitro sown seeds germinated, while the germination percentage increased up to 19% after the mechanical scarification. A further significative improvement of germination percentages was recorded after the physical scarification, with (40.5%) or without (36.5%) 8 weeks of cold stratification, especially when seeds were sown on gibberellin enriched cultured media. Vitro-derived sumac sprouts, at different developmental stages, were chemically characterized, in terms of polyphenol and tannin content, as well as for their antioxidant activity, to evaluate this matrix as a potential novel food or as a source of bioactive compounds. Results evidenced how more developed sumac sprouts and, above all, their leaves are a wealthy source of polyphenols (78.4 GAE/g SS) and tannins (21.9 mg GAE/g SS), with marked antioxidant activity. The outcomes of this study will be of support the nursery sector and sumac growers in obtaining a higher number of plants in a shorter time; moreover, the sprout chemical characterization will contribute to the process of considering this matrix as a new source of bioactive compounds and tannins to be used in food and non-food sectors.Keywords: bioactive compounds, germination pre-treatments, rhus coriaria l., tissue culture
Procedia PDF Downloads 104238 Sumac Sprouts: From in Vitro Seed Germination to Chemical Characterization
Authors: Leto Leandra, Guaitini Caterina, Agosti Anna, Del Vecchio Lorenzo, Guarrasi Valeria, Cirlini Martina, Chiancone Benedetta
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To the best of our knowledge, this study represents the first attempt to investigate the in vitro germination response of Rhus coriaria L. and its sprout chemical characterization. Rhus coriaria L., a species belonging to the Anacardiaceae family, is commonly called "sumac” and is cultivated, in different countries of the Mediterranean and the Middle East regions, to produce a spice with a sour taste, obtained from its dried and ground fruits. Moreover, since ancient times, many beneficial properties have been attributed to this plant that has been used, in the traditional medicine of several Asian countries, against various diseases, including liver and intestinal pathologies, ulcers, and various inflammatory states. In the recent past, sumac was cultivated in the Southern regions of Italy to treat leather, but its cultivation was abandoned, and currently, sumac plants grow spontaneously in marginal areas. Recently, in Italy, the interest in this species has been growing again, thanks to its numerous properties; thus, it becomes imperative to deepen the knowledge of this plant. In this study, in order to set up an efficient in vitro seed germination protocol, sumac seeds collected from spontaneous plants grown in Sicily, an island in the South of Italy, were, firstly, subjected to different treatments, scarification (mechanical, physical and chemical), cold stratification and imbibition, to break their physical and physiological dormancy, then, treated seeds were in vitro cultured on media with different gibberellic acid (GA3) concentrations. Results showed that, without any treatment, only 5% of in vitro sown seeds germinated, while the germination percentage increased up to 19% after the mechanical scarification. A further significative improvement of germination percentages was recorded after the physical scarification, with (40.5%) or without (36.5%) 8 weeks of cold stratification, especially when seeds were sown on gibberellin enriched cultured media. Vitro-derived sumac sprouts, at different developmental stages, were chemically characterized, in terms of polyphenol and tannin content, as well as for their antioxidant activity, to evaluate this matrix as a potential novel food or as a source of bioactive compounds. Results evidenced how more developed sumac sprouts and, above all, their leaves are a wealthy source of polyphenols (78.4 GAE/g SS) and tannins (21.9 mg GAE/g SS), with marked antioxidant activity. The outcomes of this study will be of support the nursery sector and sumac growers in obtaining a higher number of plants in a shorter time; moreover, the sprout chemical characterization will contribute to the process of considering this matrix as a new source of bioactive compounds and tannins to be used in food and non-food sectors.Keywords: bioactive compounds, germination pre-treatments, rhus coriaria l., tissue culture
Procedia PDF Downloads 101237 Follicular Thyroid Carcinoma in a Developing Country: A Retrospective Study of 10 Years
Authors: Abdul Aziz, Muhammad Qamar Masood, Saadia Sattar, Saira Fatima, Najmul Islam
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Introduction: The most common endocrine tumor is thyroid cancer. Follicular Thyroid Carcinoma (FTC) accounts for 5%–10% of all thyroid cancers. Patients with FTC frequently present with more advanced stage diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery, while radioactive iodine therapy is the main adjuvant therapy as per ATA guidelines. In many developing countries, surgical facilities and radioactive iodine are in short supply; therefore, understanding follicular thyroid cancer trends may help developing countries plan and use resources more effectively. Methodology: It was a retrospective observational study of FTC patients of age 18 years and above conducted at Aga Khan University Hospital, Karachi, from 1st January 2010 to 31st December 2019. Results: There were 404 patients with thyroid carcinoma, out of which forty (10.1%) were FTC. 50% of the patients were in the 41-60 years age group, and the female to male ratio was 1.5: 1. Twenty-four patients (60%) presented with complain of neck swelling followed by metastasis (20%) and compressive symptoms (20%). The most common site of metastasis was bone (87.5%), followed by lung (12.5%). The pre-operative thyroglobulin level was done in six out of eight metastatic patients (75%) in which it was elevated. This emphasizes the importance of checking thyroglobulin level in unusual presentation (bone pain, fractures) of a patient having neck swelling also to help in establishing the primary source of tumor. There was no complete documentation of ultrasound features of the thyroid gland in all the patients, which is an important investigation done in the initial evaluation of thyroid nodule. On FNAC, 50% (20 patients) had Bethesda category III-IV nodules, while 10% ( 4 patients ) had Bethesda category II. In sixteen patients, FNAC was not done as they presented with compressive symptoms or metastasis. Fifty percent had a total thyroidectomy and 50% had subtotal followed by completion thyroidectomy, plus ten patients had lymph node dissection, out of which seven had histopathological lymph node involvement. On histopathology, twenty-three patients (57.5%) had minimally invasive, while seventeen (42.5%) had widely invasive follicular thyroid carcinoma. The capsular invasion was present in thirty-three patients (82.5%); one patient had no capsular invasion, but there was a vascular invasion. Six patients' histopathology had no record of capsular invasion. In contrast, the lymphovascular invasion was present in twenty-six patients (65%). In this study, 65 % of the patients had clinical stage 1 disease, while 25% had stage 2 and 10% had clinical stage 4. Seventeen patients (42.5%) had received RAI 30-100 mCi, while ten patients (25%) received more than 100 mCi. Conclusion: FTC demographic and clinicopathological presentation are the same in Pakistan as compared to other countries. Surgery followed by RAI is the mainstay of treatment. Thus understanding the trend of FTC and proper planning and utilization of the resources will help the developing countries in effectively treating the FTC.Keywords: thyroid carcinoma, follicular thyroid carcinoma, clinicopathological features, developing countries
Procedia PDF Downloads 191236 Recent Advances in Research on Carotenoids: From Agrofood Production to Health Outcomes
Authors: Antonio J. Melendez-Martinez
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Beyond their role as natural colorants, some carotenoids are provitamins A and may be involved in health-promoting biological actions and contribute to reducing the risk of developing non-communicable diseases, including several types of cancer, cardiovascular disease, eye conditions, skin disorders or metabolic disorders. Given the versatility of carotenoids, the COST-funded European network to advance carotenoid research and applications in agro-food and health (EUROCAROTEN) is aimed at promoting health through the diet and increasing well-being by means. Stakeholders from 38 countries participate in this network, and one of its main objectives is to promote research on little-studied carotenoids. In this contribution, recent advances of our research group and collaborators in the study of two such understudied carotenoids, namely phytoene and phytofluene, the colorless carotenoids, are outlined. The study of these carotenoids is important as they have been largely neglected despite they are present in our diets, fluids, and tissues, and evidence is accumulating that they may be involved in health-promoting actions. More specifically, studies on their levels in diverse tomato and orange varieties were carried out as well as on their potential bioavailability from different dietary sources. Furthermore, the potential effect of these carotenoids on an animal model subjected to oxidative stress was evaluated. The tomatoes were grown in research greenhouses, and some of them were subjected to regulated deficit irrigation, a sustainable agronomic practice. The citrus samples were obtained from an experimental field. The levels of carotenoids were assessed using HPLC according to routine methodologies followed in our lab. Regarding the potential bioavailability (bioaccessibility) studies, different products containing colorless carotenoids, like fruits, juices, were subjected to simulated in vitro digestions, and their incorporation into mixed micelles was assessed. The effect of the carotenoids on oxidative stress was evaluated on the Caenorhabditis elegans model. For that purpose, the worms were subjected to oxidative stress by means of a hydrogen peroxide challenge. In relation to the presence of colorless carotenoids in tomatoes and orange varieties, it was observed that they are widespread in such products and that there are mutants with very high quantities of them, for instance, the Cara Cara or Pinalate mutant oranges. The studies on their bioaccessibility revealed that, in general, phytoene and phytofluene are more bioaccessible than other common dietary carotenoids, probably due to their distinctive chemical structure. About the in vivo antioxidant capacity of phytoene and phytofluene, it was observed that they both exerted antioxidant effects at certain doses. In conclusion, evidence on the importance of phytoene and phytofluene as dietary easily bioavailable and antioxidant carotenoids has been obtained in recent studies from our group, which can be important shortly to innovate in health-promotion through the development of functional foods and related products.Keywords: carotenoids, health, functional foods, nutrition, phytoene, phytofluene
Procedia PDF Downloads 103235 Predicting Susceptibility to Coronary Artery Disease using Single Nucleotide Polymorphisms with a Large-Scale Data Extraction from PubMed and Validation in an Asian Population Subset
Authors: K. H. Reeta, Bhavana Prasher, Mitali Mukerji, Dhwani Dholakia, Sangeeta Khanna, Archana Vats, Shivam Pandey, Sandeep Seth, Subir Kumar Maulik
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Introduction Research has demonstrated a connection between coronary artery disease (CAD) and genetics. We did a deep literature mining using both bioinformatics and manual efforts to identify the susceptible polymorphisms in coronary artery disease. Further, the study sought to validate these findings in an Asian population. Methodology In first phase, we used an automated pipeline which organizes and presents structured information on SNPs, Population and Diseases. The information was obtained by applying Natural Language Processing (NLP) techniques to approximately 28 million PubMed abstracts. To accomplish this, we utilized Python scripts to extract and curate disease-related data, filter out false positives, and categorize them into 24 hierarchical groups using named Entity Recognition (NER) algorithms. From the extensive research conducted, a total of 466 unique PubMed Identifiers (PMIDs) and 694 Single Nucleotide Polymorphisms (SNPs) related to coronary artery disease (CAD) were identified. To refine the selection process, a thorough manual examination of all the studies was carried out. Specifically, SNPs that demonstrated susceptibility to CAD and exhibited a positive Odds Ratio (OR) were selected, and a final pool of 324 SNPs was compiled. The next phase involved validating the identified SNPs in DNA samples of 96 CAD patients and 37 healthy controls from Indian population using Global Screening Array. ResultsThe results exhibited out of 324, only 108 SNPs were expressed, further 4 SNPs showed significant difference of minor allele frequency in cases and controls. These were rs187238 of IL-18 gene, rs731236 of VDR gene, rs11556218 of IL16 gene and rs5882 of CETP gene. Prior researches have reported association of these SNPs with various pathways like endothelial damage, susceptibility of vitamin D receptor (VDR) polymorphisms, and reduction of HDL-cholesterol levels, ultimately leading to the development of CAD. Among these, only rs731236 had been studied in Indian population and that too in diabetes and vitamin D deficiency. For the first time, these SNPs were reported to be associated with CAD in Indian population. Conclusion: This pool of 324 SNP s is a unique kind of resource that can help to uncover risk associations in CAD. Here, we validated in Indian population. Further, validation in different populations may offer valuable insights and contribute to the development of a screening tool and may help in enabling the implementation of primary prevention strategies targeted at the vulnerable population.Keywords: coronary artery disease, single nucleotide polymorphism, susceptible SNP, bioinformatics
Procedia PDF Downloads 76234 The Elimination of Fossil Fuel Subsidies from the Road Transportation Sector and the Promotion of Electro Mobility: The Ecuadorian Case
Authors: Henry Gonzalo Acurio Flores, Alvaro Nicolas Corral Naveda, Juan Francisco Fonseca Palacios
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In Ecuador, subventions on fossil fuels for the road transportation sector have always been part of its economy throughout time, mainly because of demagogy and populism from political leaders. It is clearly seen that the government cannot maintain the subsidies anymore due to its commercial balance and its general state budget; subsidies are a key barrier to implementing the use of cleaner technologies. However, during the last few months, the elimination of subsidies has been done gradually with the purpose of reaching international prices. It is expected that with this measure, the population will opt for other means of transportation, and in a certain way, it will promote the use of private electric vehicles and public, e.g., taxis and buses (urban transport). Considering the three main elements of sustainable development, an analysis of the social, economic, and environmental impacts of eliminating subsidies will be generated at the country level. To achieve this, four scenarios will be developed in order to determine how the subsidies will contribute to the promotion of electro-mobility. 1) A Business as Usual BAU scenario; 2) the introduction of 10 000 electric vehicles by 2025; 3) the introduction of 100 000 electric vehicles by 2030; 4) the introduction of 750 000 electric vehicles by 2040 (for all the scenarios buses, taxis, lightweight duty vehicles, and private vehicles will be introduced, as it is established in the National Electro Mobility Strategy for Ecuador). The Low Emissions Analysis Platform (LEAP) will be used, and it will be suitable to determine the cost for the government in terms of importing derivatives for fossil fuels and the cost of electricity to power the electric fleet that can be changed. The elimination of subventions generates fiscal resources for the state that can be used to develop other kinds of projects that will benefit Ecuadorian society. It will definitely change the energy matrix, and it will provide energy security for the country; it will be an opportunity for the government to incentivize a greater introduction of renewable energies, e.g., solar, wind, and geothermal. At the same time, it will also reduce greenhouse gas emissions (GHG) from the transportation sector, considering its mitigation potential, which as a result, will ameliorate the inhabitant quality of life by improving the quality of air, therefore reducing respiratory diseases associated with exhaust emissions, consequently, achieving sustainability, the Sustainable Development Goals (SDGs), and complying with the agreements established in the Paris Agreement COP 21 in 2015. Electro mobility in Latin America and the Caribbean can only be achieved by the implementation of the right policies at the central government, which need to be accompanied by a National Urban Mobility Policy (NUMP) and can encompass a greater vision to develop holistic, sustainable transport systems at local governments.Keywords: electro mobility, energy, policy, sustainable transportation
Procedia PDF Downloads 84233 The Type II Immune Response in Acute and Chronic Pancreatitis Mediated by STAT6 in Murine
Authors: Hager Elsheikh
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Context: Pancreatitis is a condition characterized by inflammation in the pancreas, which can lead to serious complications if untreated. Both acute and chronic pancreatitis are associated with immune reactions and fibrosis, which further damage the pancreas. The type 2 immune response, primarily driven by alternative activated macrophages (AAMs), plays a significant role in the development of fibrosis. The IL-4/STAT6 pathway is a crucial signaling pathway for the activation of M2 macrophages. Pancreatic fibrosis is induced by dysregulated inflammatory responses and can result in the autodigestion and necrosis of pancreatic acinar cells. Research Aim: The aim of this study is to investigate the impact of STAT6, a crucial molecule in the IL-4/STAT6 pathway, on the severity and development of fibrosis during acute and chronic pancreatitis. The research also aims to understand the influence of the JAK/STAT6 signaling pathway on the balance between fibrosis and regeneration in the presence of different macrophage populations. Methodology: The research utilizes murine models of acute and chronic pancreatitis induced by cerulean injection. Animal models will be employed to study the effect of STAT6 knockout on disease severity and fibrosis. Isolation of acinar cells and cell culture techniques will be used to assess the impact of different macrophage populations on wound healing and regeneration. Various techniques such as PCR, histology, immunofluorescence, and transcriptomics will be employed to analyze the tissues and cells. Findings: The research aims to provide insights into the mechanisms underlying tissue fibrosis and wound healing during acute and chronic pancreatitis. By investigating the influence of the JAK/STAT6 signaling pathway and different macrophage populations, the study aims to understand their impact on tissue fibrosis, disease severity, and pancreatic regeneration. Theoretical Importance: This research contributes to our understanding of the role of specific signaling pathways, macrophage polarization, and the type 2 immune response in pancreatitis. It provides insights into the molecular mechanisms underlying tissue fibrosis and the potential for targeted therapies. Data Collection and Analysis Procedures: Data will be collected through the use of murine models, isolation and culture of acinar cells, and various experimental techniques such as PCR, histology, immunofluorescence, and transcriptomics. Data will be analyzed using appropriate statistical methods and techniques, and the findings will be interpreted in the context of the research objectives. Conclusion: By investigating the mechanisms of tissue fibrosis and wound healing during acute and chronic pancreatitis, this research aims to enhance our understanding of the disease progression and potential therapeutic targets. The findings have theoretical importance in expanding our knowledge of pancreatic fibrosis and the role of macrophage polarization in the context of the type 2 immune response.Keywords: immunity in chronic diseases, pancreatitis, macrophages, immune response
Procedia PDF Downloads 33232 Magnetic SF (Silk Fibroin) E-Gel Scaffolds Containing bFGF-Conjugated Fe3O4 Nanoparticles
Authors: Z. Karahaliloğlu, E. Yalçın, M. Demirbilek, E.B. Denkbaş
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Critical-sized bone defects caused by trauma, bone diseases, prosthetic implant revision or tumor excision cannot be repaired by physiological regenerative processes. Current orthopedic applications for critical-sized bone defects are to use autologous bone grafts, bone allografts, or synthetic graft materials. However, these strategies are unable to solve completely the problem, and motivate the development of novel effective biological scaffolds for tissue engineering applications and regenerative medicine applications. In particular, scaffolds combined with a variety of bio-agents as fundamental tools emerge to provide the regeneration of damaged bone tissues due to their ability to promote cell growth and function. In this study, a magnetic silk fibroin (SF) hydrogel scaffold was prepared by electrogelation process of the concentrated Bombxy mori silk fibroin (8 %wt) aqueous solution. For enhancement of osteoblast-like cells (SaOS-2) growth and adhesion, basal fibroblast growth factor (bFGF) were conjugated physically to the HSA-coated magnetic nanoparticles (Fe3O4) and magnetic SF e-gel scaffolds were prepared by incorporation of Fe3O4, HSA (human serum albumin)=Fe3O4 and HSA=Fe3O4-bFGF nanoparticles. HSA=Fe3O4, HSA=Fe3O4-bFGF loaded and bare SF e-gels scaffolds were characterized using scanning electron microscopy (SEM.) For cell studies, human osteoblast-like cell line (SaOS-2) was used and an MTT assay was used to assess the cytotoxicity of magnetic silk fibroin e-gel scaffolds and cell density on these surfaces. For the evaluation osteogenic activation, ALP (alkaline phosphatase), the amount of mineralized calcium, total protein and collagen were studied. Fe3O4 nanoparticles were successfully synthesized and bFGF was conjugated to HSA=Fe3O4 nanoparticles with %97.5 of binding yield which has a particle size of 71.52±2.3 nm. Electron microscopy images of the prepared HSA and bFGF incorporated SF e-gel scaffolds showed a 3D porous morphology. In terms of water uptake results, bFGF conjugated HSA=Fe3O4 nanoparticles has the best water absorbability behavior among all groups. In the in-vitro cell culture studies realized using SaOS-2 cell line, the coating of Fe3O4 nanoparticles surface with a protein enhance the cell viability and HSA coating and bFGF conjugation, the both have an inductive effect in the cell proliferation. One of the markers of bone formation and osteoblast differentiation, according to the ALP activity and total protein results, HSA=Fe3O4-bFGF loaded SF e-gels had significantly enhanced ALP activity. Osteoblast cultured HSA=Fe3O4-bFGF loaded SF e-gels deposited more calcium compared with SF e-gel. The proposed magnetic scaffolds seem to be promising for bone tissue regeneration and used in future work for various applications.Keywords: basic fibroblast growth factor (bFGF), e-gel, iron oxide nanoparticles, silk fibroin
Procedia PDF Downloads 288231 Predictors of Sexually Transmitted Infection of Korean Adolescent Females: Analysis of Pooled Data from Korean Nationwide Survey
Authors: Jaeyoung Lee, Minji Je
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Objectives: In adolescence, adolescents are curious about sex, but sexual experience before becoming an adult can cause the risk of high probability of sexually transmitted infection. Therefore, it is very important to prevent sexually transmitted infections so that adolescents can grow in healthy and upright way. Adolescent females, especially, have sexual behavior distinguished from that of male adolescents. Protecting female adolescents’ reproductive health is even more important since it is directly related to the childbirth of the next generation. This study, thus, investigated the predictors of sexually transmitted infection in adolescent females with sexual experiences based on the National Health Statistics in Korea. Methods: This study was conducted based on the National Health Statistics in Korea. The 11th Korea Youth Behavior Web-based Survey in 2016 was conducted in the type of anonymous self-reported survey in order to find out the health behavior of adolescents. The target recruitment group was middle and high school students nationwide as of April 2016, and 65,528 students from a total of 800 middle and high schools participated. The study was conducted in 537 female high school students (Grades 10–12) among them. The collected data were analyzed as complex sampling design using SPSS statistics 22. The strata, cluster, weight, and finite population correction provided by Korea Center for Disease Control & Prevention (KCDC) were reflected to constitute complex sample design files, which were used in the statistical analysis. The analysis methods included Rao-Scott chi-square test, complex samples general linear model, and complex samples multiple logistic regression analysis. Results: Out of 537 female adolescents, 11.9% (53 adolescents) had experiences of venereal infection. The predictors for venereal infection of the subjects were ‘age at first intercourse’ and ‘sexual intercourse after drinking’. The sexually transmitted infection of the subjects was decreased by 0.31 times (p=.006, 95%CI=0.13-0.71) for middle school students and 0.13 times (p<.001, 95%CI=0.05-0.32) for high school students whereas the age of the first sexual experience was under elementary school age. In addition, the sexually transmitted infection of the subjects was 3.54 times (p < .001, 95%CI=1.76-7.14) increased when they have experience of sexual relation after drinking alcohol, compared to those without the experience of sexual relation after drinking alcohol. Conclusions: The female adolescents had high probability of sexually transmitted infection if their age for the first sexual experience was low. Therefore, the female adolescents who start sexual experience earlier shall have practical sex education appropriate for their developmental stage. In addition, since the sexually transmitted infection increases, if they have sexual relations after drinking alcohol, the consideration for prevention of alcohol use or intervention of sex education shall be required. When health education intervention is conducted for health promotion for female adolescents in the future, it is necessary to reflect the result of this study.Keywords: adolescent, coitus, female, sexually transmitted diseases
Procedia PDF Downloads 192230 Inhibition of Food Borne Pathogens by Bacteriocinogenic Enterococcus Strains
Authors: Neha Farid
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Due to the abuse of antimicrobial medications in animal feed, the occurrence of multi-drug resistant (MDR) pathogens in foods is currently a growing public health concern on a global scale. MDR infections have the potential to penetrate the food chain by posing a serious risk to both consumers and animals. Food pathogens are those biological agents that have the tendency to cause pathogenicity in the host body upon ingestion. The major reservoirs of foodborne pathogens include food-producing fauna like cows, pigs, goats, sheep, deer, etc. The intestines of these animals are highly condensed with several different types of food pathogens. Bacterial food pathogens are the main cause of foodborne disease in humans; almost 66% of the reported cases of food illness in a year are caused by the infestation of bacterial food pathogens. When ingested, these pathogens reproduce and survive or form different kinds of toxins inside host cells causing severe infections. The genus Listeria consists of gram-positive, rod-shaped, non-spore-forming bacteria. The disease caused by Listeria monocytogenes is listeriosis or gastroenteritis, which induces fever, vomiting, and severe diarrhea in the affected body. Campylobacter jejuni is a gram-negative, curved-rod-shaped bacteria causing foodborne illness. The major source of Campylobacter jejuni is livestock and poultry; particularly, chicken is highly colonized with Campylobacter jejuni. Serious public health concerns include the widespread growth of bacteria that are resistant to antibiotics and the slowing in the discovery of new classes of medicines. The objective of this study is to provide some potential antibacterial activities with certain broad-range antibiotics and our desired bacteriocins, i.e., Enterococcus faecium from specific strains preventing microbial contamination pathways in order to safeguard the food by lowering food deterioration, contamination, and foodborne illnesses. The food pathogens were isolated from various sources of dairy products and meat samples. The isolates were tested for the presence of Listeria and Campylobacter by gram staining and biochemical testing. They were further sub-cultured on selective media enriched with the growth supplements for Listeria and Campylobacter. All six strains of Listeria and Campylobacter were tested against ten antibiotics. Campylobacter strains showed resistance against all the antibiotics, whereas Listeria was found to be resistant only against Nalidixic Acid and Erythromycin. Further, the strains were tested against the two bacteriocins isolated from Enterococcus faecium. It was found that bacteriocins showed better antimicrobial activity against food pathogens. They can be used as a potential antimicrobial for food preservation. Thus, the study concluded that natural antimicrobials could be used as alternatives to synthetic antimicrobials to overcome the problem of food spoilage and severe food diseases.Keywords: food pathogens, listeria, campylobacter, antibiotics, bacteriocins
Procedia PDF Downloads 71229 A Correlations Study on Nursing Staff's Shifts Systems, Workplace Fatigue, and Quality of Working Life
Authors: Jui Chen Wu, Ming Yi Hsu
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Background and Purpose: Shift work of nursing staff is inevitable in hospital to provide continuing medical care. However, shift work is considered as a health hazard that may cause physical and psychological problems. Serious workplace fatigue of nursing shift work might impact on family, social and work life, moreover, causes serious reduction of quality of medical care, or even malpractice. This study aims to explore relationships among nursing staff’s shift, workplace fatigue and quality of working life. Method: Structured questionnaires were used in this study to explore relationships among shift work, workplace fatigue and quality of working life in nursing staffs. We recruited 590 nursing staffs in different Community Teaching hospitals in Taiwan. Data analysed by descriptive statistics, single sample t-test, single factor analysis, Pearson correlation coefficient and hierarchical regression, etc. Results: The overall workplace fatigue score is 50.59 points. In further analysis, the score of personal burnout, work-related burnout, over-commitment and client-related burnout are 57.86, 53.83, 45.95 and 44.71. The basic attributes of nursing staff are significantly different from those of workplace fatigue with different ages, licenses, sleeping quality, self-conscious health status, number of care patients of chronic diseases and number of care people in the obstetric ward. The shift variables revealed no significant influence on workplace fatigue during the hierarchical regression analysis. About the analysis on nursing staff’s basic attributes and shift on the quality of working life, descriptive results show that the overall quality of working life of nursing staff is 3.23 points. Comparing the average score of the six aspects, the ranked average score are 3.47 (SD= .43) in interrelationship, 3.40 (SD= .46) in self-actualisation, 3.30 (SD= .40) in self-efficacy, 3.15 (SD= .38) in vocational concept, 3.07 (SD= .37) in work aspects, and 3.02 (SD= .56) in organization aspects. The basic attributes of nursing staff are significantly different from quality of working life in different marriage situations, education level, years of nursing work, occupation area, sleep quality, self-conscious health status and number of care in medical ward. There are significant differences between shift mode and shift rate with the quality of working life. The results of the hierarchical regression analysis reveal that one of the shifts variables 'shift mode' which does affect staff’s quality of working life. The workplace fatigue is negatively correlated with the quality of working life, and the over-commitment in the workplace fatigue is positively related to the vocational concept of the quality of working life. According to the regression analysis of nursing staff’s basic attributes, shift mode, workplace fatigue and quality of working life related shift, the results show that the workplace fatigue has a significant impact on nursing staff’s quality of working life. Conclusion: According to our study, shift work is correlated with workplace fatigue in nursing staffs. This results work as important reference for human resources management in hospitals to establishing a more positive and healthy work arrangement policy.Keywords: nursing staff, shift, workplace fatigue, quality of working life
Procedia PDF Downloads 272228 The Role of Piceatannol in Counteracting Glyceraldehyde-3-Phosphate Dehydrogenase Aggregation and Nuclear Translocation
Authors: Joanna Gerszon, Aleksandra Rodacka
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In the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein and peptide aggregation processes play a vital role in contributing to the formation of intracellular and extracellular protein deposits. One of the major components of these deposits is the oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Therefore, the purpose of this research was to answer the question whether piceatannol, a stilbene derivative, counteracts and/or slows down oxidative stress-induced GAPDH aggregation. The study also aimed to determine if this natural occurring compound prevents unfavorable nuclear translocation of GAPDH in hippocampal cells. The isothermal titration calorimetry (ITC) analysis indicated that one molecule of GAPDH can bind up to 8 molecules of piceatannol (7.3 ± 0.9). As a consequence of piceatannol binding to the enzyme, the loss of activity was observed. Parallel with GAPDH inactivation the changes in zeta potential, and loss of free thiol groups were noted. Nevertheless, the ligand-protein binding does not influence the secondary structure of the GAPDH. Precise molecular docking analysis of the interactions inside the active center allowed to presume that these effects are due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Molecular docking also showed that simultaneously 11 molecules of ligand can be bound to dehydrogenase. Taking into consideration obtained data, the influence of piceatannol on level of GAPDH aggregation induced by excessive oxidative stress was examined. The applied methods (thioflavin-T binding-dependent fluorescence as well as microscopy methods - transmission electron microscopy, Congo Red staining) revealed that piceatannol significantly diminishes level of GAPDH aggregation. Finally, studies involving cellular model (Western blot analyses of nuclear and cytosolic fractions and confocal microscopy) indicated that piceatannol-GAPDH binding prevents GAPDH from nuclear translocation induced by excessive oxidative stress in hippocampal cells. In consequence, it counteracts cell apoptosis. These studies demonstrate that by binding with GAPDH, piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation as well as it prevents hippocampal cells from apoptosis by retaining GAPDH in the cytoplasm. All these findings provide a new insight into the role of piceatannol interaction with GAPDH and present a potential therapeutic strategy for some neurological disorders related to GAPDH aggregation. This work was supported by the by National Science Centre, Poland (grant number 2017/25/N/NZ1/02849).Keywords: glyceraldehyde-3-phosphate dehydrogenase, neurodegenerative disease, neuroprotection, piceatannol, protein aggregation
Procedia PDF Downloads 167227 Integration of a Protective Film to Enhance the Longevity and Performance of Miniaturized Ion Sensors
Authors: Antonio Ruiz Gonzalez, Kwang-Leong Choy
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The measurement of electrolytes has a high value in the clinical routine. Ions are present in all body fluids with variable concentrations and are involved in multiple pathologies such as heart failures and chronic kidney disease. In the case of dissolved potassium, although a high concentration in the blood (hyperkalemia) is relatively uncommon in the general population, it is one of the most frequent acute electrolyte abnormalities. In recent years, the integration of thin films technologies in this field has allowed the development of highly sensitive biosensors with ultra-low limits of detection for the assessment of metals in liquid samples. However, despite the current efforts in the miniaturization of sensitive devices and their integration into portable systems, only a limited number of successful examples used commercially can be found. This fact can be attributed to a high cost involved in their production and the sustained degradation of the electrodes over time, which causes a signal drift in the measurements. Thus, there is an unmet necessity for the development of low-cost and robust sensors for the real-time monitoring of analyte concentrations in patients to allow the early detection and diagnosis of diseases. This paper reports a thin film ion-selective sensor for the evaluation of potassium ions in aqueous samples. As an alternative for this fabrication method, aerosol assisted chemical vapor deposition (AACVD), was applied due to cost-effectivity and fine control over the film deposition. Such a technique does not require vacuum and is suitable for the coating of large surface areas and structures with complex geometries. This approach allowed the fabrication of highly homogeneous surfaces with well-defined microstructures onto 50 nm thin gold layers. The degradative processes of the ubiquitously employed poly (vinyl chloride) membranes in contact with an electrolyte solution were studied, including the polymer leaching process, mechanical desorption of nanoparticles and chemical degradation over time. Rational design of a protective coating based on an organosilicon material in combination with cellulose to improve the long-term stability of the sensors was then carried out, showing an improvement in the performance after 5 weeks. The antifouling properties of such coating were assessed using a cutting-edge quartz microbalance sensor, allowing the quantification of the adsorbed proteins in the nanogram range. A correlation between the microstructural properties of the films with the surface energy and biomolecules adhesion was then found and used to optimize the protective film.Keywords: hyperkalemia, drift, AACVD, organosilicon
Procedia PDF Downloads 123226 Production of Bacillus Lipopeptides for Biocontrol of Postharvest Crops
Authors: Vivek Rangarajan, Kim G. Klarke
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With overpopulation threatening the world’s ability to feed itself, food production and protection has become a major issue, especially in developing countries. Almost one-third of the food produced for human consumption, around 1.3 billion tonnes, is either wasted or lost annually. Postharvest decay in particular constitutes a major cause of crop loss with about 20% of fruits and vegetables produced lost during postharvest storage, mainly due to fungal disease. Some of the major phytopathogenic fungi affecting postharvest fruit crops in South Africa include Aspergillus, Botrytis, Penicillium, Alternaria and Sclerotinia spp. To date control of fungal phytopathogens has primarily been dependent on synthetic chemical fungicides, but these chemicals pose a significant threat to the environment, mainly due to their xenobiotic properties and tendency to generate resistance in the phytopathogens. Here, an environmentally benign alternative approach to control postharvest fungal phytopathogens in perishable fruit crops has been presented, namely the application of a bio-fungicide in the form of lipopeptide molecules. Lipopeptides are biosurfactants produced by Bacillus spp. which have been established as green, nontoxic and biodegradable molecules with antimicrobial properties. However, since the Bacillus are capable of producing a large number of lipopeptide homologues with differing efficacies against distinct target organisms, the lipopeptide production conditions and strategy are critical to produce the maximum lipopeptide concentration with homologue ratios to specification for optimum bio-fungicide efficacy. Process conditions, and their impact on Bacillus lipopeptide production, were evaluated in fully instrumented laboratory scale bioreactors under well-regulated controlled and defined environments. Factors such as the oxygen availability and trace element and nitrate concentrations had profound influences on lipopeptide yield, productivity and selectivity. Lipopeptide yield and homologue selectivity were enhanced in cultures where the oxygen in the sparge gas was increased from 21 to 30 mole%. The addition of trace elements, particularly Fe2+, increased the total concentration of lipopeptides and a nitrate concentration equivalent to 8 g/L ammonium nitrate resulted in optimum lipopeptide yield and homologue selectivity. Efficacy studies of the culture supernatant containing the crude lipopeptide mixture were conducted using phytopathogens isolated from fruit in the field, identified using genetic sequencing. The supernatant exhibited antifungal activity against all the test-isolates, namely Lewia, Botrytis, Penicillium, Alternaria and Sclerotinia spp., even in this crude form. Thus the lipopeptide product efficacy has been confirmed to control the main diseases, even in the basic crude form. Future studies will be directed towards purification of the lipopeptide product and enhancement of efficacy.Keywords: antifungal efficacy, biocontrol, lipopeptide production, perishable crops
Procedia PDF Downloads 404225 Spatial Variability of Soil Metal Contamination to Detect Cancer Risk Zones in Coimbatore Region of India
Authors: Aarthi Mariappan, Janani Selvaraj, P. B. Harathi, M. Prashanthi Devi
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Anthropogenic modification of the urban environment has largely increased in the recent years in order to sustain the growing human population. Intense industrial activity, permanent and high traffic on the roads, a developed subterranean infrastructure network, land use patterns are just some specific characteristics. Every day, the urban environment is polluted by more or less toxic emissions, organic or metals wastes discharged from specific activities such as industrial, commercial, municipal. When these eventually deposit into the soil, the physical and chemical properties of the surrounding soil is changed, transforming it into a human exposure indicator. Metals are non-degradable and occur cumulative in soil due to regular deposits are a result of permanent human activity. Due to this, metals are a contaminant factor for soil when persistent over a long period of time and a possible danger for inhabitant’s health on prolonged exposure. Metals accumulated in contaminated soil may be transferred to humans directly, by inhaling the dust raised from top soil, or by ingesting, or by dermal contact and indirectly, through plants and animals grown on contaminated soil and used for food. Some metals, like Cu, Mn, Zn, are beneficial for human’s health and represent a danger only if their concentration is above permissible levels, but other metals, like Pb, As, Cd, Hg, are toxic even at trace level causing gastrointestinal and lung cancers. In urban areas, metals can be emitted from a wide variety of sources like industrial, residential, commercial activities. Our study interrogates the spatial distribution of heavy metals in soil in relation to their permissible levels and their association with the health risk to the urban population in Coimbatore, India. Coimbatore region is a high cancer risk zone and case records of gastro intestinal and respiratory cancer patients were collected from hospitals and geocoded in ArcGIS10.1. The data of patients pertaining to the urban limits were retained and checked for their diseases history based on their diagnosis and treatment. A disease map of cancer was prepared to show the disease distribution. It has been observed that in our study area Cr, Pb, As, Fe and Mg exceeded their permissible levels in the soil. Using spatial overlay analysis a relationship between environmental exposure to these potentially toxic elements in soil and cancer distribution in Coimbatore district was established to show areas of cancer risk. Through this, our study throws light on the impact of prolonged exposure to soil contamination in soil in the urban zones, thereby exploring the possibility to detect cancer risk zones and to create awareness among the exposed groups on cancer risk.Keywords: soil contamination, cancer risk, spatial analysis, India
Procedia PDF Downloads 403224 Fractional, Component and Morphological Composition of Ambient Air Dust in the Areas of Mining Industry
Authors: S.V. Kleyn, S.Yu. Zagorodnov, А.А. Kokoulina
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Technogenic emissions of the mining and processing complex are characterized by a high content of chemical components and solid dust particles. However, each industrial enterprise and the surrounding area have features that require refinement and parameterization. Numerous studies have shown the negative impact of fine dust PM10 and PM2.5 on the health, as well as the possibility of toxic components absorption, including heavy metals by dust particles. The target of the study was the quantitative assessment of the fractional and particle size composition of ambient air dust in the area of impact by primary magnesium production complex. Also, we tried to describe the morphology features of dust particles. Study methods. To identify the dust emission sources, the analysis of the production process has been carried out. The particulate composition of the emissions was measured using laser particle analyzer Microtrac S3500 (covered range of particle size is 20 nm to 2000 km). Particle morphology and the component composition were established by electron microscopy by scanning microscope of high resolution (magnification rate - 5 to 300 000 times) with X-ray fluorescence device S3400N ‘HITACHI’. The chemical composition was identified by X-ray analysis of the samples using an X-ray diffractometer XRD-700 ‘Shimadzu’. Determination of the dust pollution level was carried out using model calculations of emissions in the atmosphere dispersion. The calculations were verified by instrumental studies. Results of the study. The results demonstrated that the dust emissions of different technical processes are heterogeneous and fractional structure is complicated. The percentage of particle sizes up to 2.5 micrometres inclusive was ranged from 0.00 to 56.70%; particle sizes less than 10 microns inclusive – 0.00 - 85.60%; particle sizes greater than 10 microns - 14.40% -100.00%. During microscopy, the presence of nanoscale size particles has been detected. Studied dust particles are round, irregular, cubic and integral shapes. The composition of the dust includes magnesium, sodium, potassium, calcium, iron, chlorine. On the base of obtained results, it was performed the model calculations of dust emissions dispersion and establishment of the areas of fine dust РМ 10 and РМ 2.5 distribution. It was found that the dust emissions of fine powder fractions PM10 and PM2.5 are dispersed over large distances and beyond the border of the industrial site of the enterprise. The population living near the enterprise is exposed to the risk of diseases associated with dust exposure. Data are transferred to the economic entity to make decisions on the measures to minimize the risks. Exposure and risks indicators on the health are used to provide named patient health and preventive care to the citizens living in the area of negative impact of the facility.Keywords: dust emissions, еxposure assessment, PM 10, PM 2.5
Procedia PDF Downloads 261223 Frailty and Quality of Life among Older Adults: A Study of Six LMICs Using SAGE Data
Authors: Mamta Jat
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Background: The increased longevity has resulted in the increase in the percentage of the global population aged 60 years or over. With this “demographic transition” towards ageing, “epidemiologic transition” is also taking place characterised by growing share of non-communicable diseases in the overall disease burden. So, many of the older adults are ageing with chronic disease and high levels of frailty which often results in lower levels of quality of life. Although frailty may be increasingly common in older adults, prevention or, at least, delay the onset of late-life adverse health outcomes and disability is necessary to maintain the health and functional status of the ageing population. This is an effort using SAGE data to assess levels of frailty and its socio-demographic correlates and its relation with quality of life in LMICs of India, China, Ghana, Mexico, Russia and South Africa in a comparative perspective. Methods: The data comes from multi-country Study on Global AGEing and Adult Health (SAGE), consists of nationally representative samples of older adults in six low and middle-income countries (LMICs): China, Ghana, India, Mexico, the Russian Federation and South Africa. For our study purpose, we will consider only 50+ year’s respondents. The logistic regression model has been used to assess the correlates of frailty. Multinomial logistic regression has been used to study the effect of frailty on QOL (quality of life), controlling for the effect of socio-economic and demographic correlates. Results: Among all the countries India is having highest mean frailty in males (0.22) and females (0.26) and China with the lowest mean frailty in males (0.12) and females (0.14). The odds of being frail are more likely with the increase in age across all the countries. In India, China and Russia the chances of frailty are more among rural older adults; whereas, in Ghana, South Africa and Mexico rural residence is protecting against frailty. Among all countries china has high percentage (71.46) of frail people in low QOL; whereas Mexico has lowest percentage (36.13) of frail people in low QOL.s The risk of having low and middle QOL is significantly (p<0.001) higher among frail elderly as compared to non–frail elderly across all countries with controlling socio-demographic correlates. Conclusion: Women and older age groups are having higher frailty levels than men and younger aged adults in LMICs. The mean frailty scores demonstrated a strong inverse relationship with education and income gradients, while lower levels of education and wealth are showing higher levels of frailty. These patterns are consistent across all LMICs. These data support a significant role of frailty with all other influences controlled, in having low QOL as measured by WHOQOL index. Future research needs to be built on this evolving concept of frailty in an effort to improve quality of life for frail elderly population, in LMICs setting.Keywords: Keywords: Ageing, elderly, frailty, quality of life
Procedia PDF Downloads 287222 Implementing the WHO Air Quality Guideline for PM2.5 Worldwide can Prevent Millions of Premature Deaths Per Year
Authors: Despina Giannadaki, Jos Lelieveld, Andrea Pozzer, John Evans
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Outdoor air pollution by fine particles ranks among the top ten global health risk factors that can lead to premature mortality. Epidemiological cohort studies, mainly conducted in United States and Europe, have shown that the long-term exposure to PM2.5 (particles with an aerodynamic diameter less than 2.5μm) is associated with increased mortality from cardiovascular, respiratory diseases and lung cancer. Fine particulates can cause health impacts even at very low concentrations. Previously, no concentration level has been defined below which health damage can be fully prevented. The World Health Organization ambient air quality guidelines suggest an annual mean PM2.5 concentration limit of 10μg/m3. Populations in large parts of the world, especially in East and Southeast Asia, and in the Middle East, are exposed to high levels of fine particulate pollution that by far exceeds the World Health Organization guidelines. The aim of this work is to evaluate the implementation of recent air quality standards for PM2.5 in the EU, the US and other countries worldwide and estimate what measures will be needed to substantially reduce premature mortality. We investigated premature mortality attributed to fine particulate matter (PM2.5) under adults ≥ 30yrs and children < 5yrs, applying a high-resolution global atmospheric chemistry model combined with epidemiological concentration-response functions. The latter are based on the methodology of the Global Burden of Disease for 2010, assuming a ‘safe’ annual mean PM2.5 threshold of 7.3μg/m3. We estimate the global premature mortality by PM2.5 at 3.15 million/year in 2010. China is the leading country with about 1.33 million, followed by India with 575 thousand and Pakistan with 105 thousand. For the European Union (EU) we estimate 173 thousand and the United States (US) 52 thousand in 2010. Based on sensitivity calculations we tested the gains from PM2.5 control by applying the air quality guidelines (AQG) and standards of the World Health Organization (WHO), the EU, the US and other countries. To estimate potential reductions in mortality rates we take into consideration the deaths that cannot be avoided after the implementation of PM2.5 upper limits, due to the contribution of natural sources to total PM2.5 and therefore to mortality (mainly airborne desert dust). The annual mean EU limit of 25μg/m3 would reduce global premature mortality by 18%, while within the EU the effect is negligible, indicating that the standard is largely met and that stricter limits are needed. The new US standard of 12μg/m3 would reduce premature mortality by 46% worldwide, 4% in the US and 20% in the EU. Implementing the AQG by the WHO of 10μg/m3 would reduce global premature mortality by 54%, 76% in China and 59% in India. In the EU and US, the mortality would be reduced by 36% and 14%, respectively. Hence, following the WHO guideline will prevent 1.7 million premature deaths per year. Sensitivity calculations indicate that even small changes at the lower PM2.5 standards can have major impacts on global mortality rates.Keywords: air quality guidelines, outdoor air pollution, particulate matter, premature mortality
Procedia PDF Downloads 310221 The Possible Interaction between Bisphenol A, Caffeine and Epigallocatechin-3-Gallate on Neurotoxicity Induced by Manganese in Rats
Authors: Azza A. Ali, Hebatalla I. Ahmed, Asmaa Abdelaty
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Background: Manganese (Mn) is a naturally occurring element. Exposure to high levels of Mn causes neurotoxic effects and represents an environmental risk factor. Mn neurotoxicity is poorly understood but changing of AChE activity, monoamines and oxidative stress has been established. Bisphenol A (BPA) is a synthetic compound widely used in the production of polycarbonate plastics. There is considerable debate about whether its exposure represents an environmental risk. Caffeine is one of the major contributors to the dietary antioxidants which prevent oxidative damage and may reduce the risk of chronic neurodegenerative diseases. Epigallocatechin-3-gallate is another major component of green tea and has known interactions with caffeine. It also has health-promoting effects in CNS. Objective: To evaluate the potential protective effects of Caffeine and/or EGCG against Mn-induced neurotoxicity either alone or in the presence of BPA in rats. Methods: Seven groups of rats were used and received daily for 5 weeks MnCl2.4H2O (10 mg/kg, IP) except the control group which received saline, corn oil and distilled H2O. Mn was injected either alone or in combination with each of the following: BPA (50 mg/kg, PO), caffeine (10 mg/kg, PO), EGCG (5 mg/kg, IP), caffeine + EGCG and BPA +caffeine +EGCG. All rats were examined in five behavioral tests (grid, bar, swimming, open field and Y- maze tests). Biochemical changes in monoamines, caspase-3, PGE2, GSK-3B, glutamate, acetyl cholinesterase and oxidative parameters, as well as histopathological changes in the brain, were also evaluated for all groups. Results: Mn significantly increased MDA and nitrite content as well as caspase-3, GSK-3B, PGE2 and glutamate levels while significantly decreased TAC and SOD as well as cholinesterase in the striatum. It also decreased DA, NE and 5-HT levels in the striatum and frontal cortex. BPA together with Mn enhanced oxidative stress generation induced by Mn while increased monoamine content that was decreased by Mn in rat striatum. BPA abolished neuronal degeneration induced by Mn in the hippocampus but not in the substantia nigra, striatum and cerebral cortex. Behavioral examinations showed that caffeine and EGCG co-administration had more pronounced protective effect against Mn-induced neurotoxicity than each one alone. EGCG alone or in combination with caffeine prevented neuronal degeneration in the substantia nigra, striatum, hippocampus and cerebral cortex induced by Mn while caffeine alone prevented neuronal degeneration in the substantia nigra and striatum but still showed some nuclear pyknosis in cerebral cortex and hippocampus. The marked protection of caffeine and EGCG co-administration also confirmed by the significant increase in TAC, SOD, ACHE, DA, NE and 5-HT as well as the decrease in MDA, nitrite, caspase-3, PGE2, GSK-3B, the glutamic acid in the striatum. Conclusion: Neuronal degeneration induced by Mn showed some inhibition with BPA exposure despite the enhancement in oxidative stress generation. Co-administration of EGCG and caffeine can protect against neuronal degeneration induced by Mn and improve behavioral deficits associated with its neurotoxicity. The protective effect of EGCG was more pronounced than that of caffeine even with BPA co-exposure.Keywords: manganese, bisphenol a, caffeine, epigallocatechin-3-gallate, neurotoxicity, behavioral tests, rats
Procedia PDF Downloads 228220 COVID-19 Laws and Policy: The Use of Policy Surveillance For Better Legal Preparedness
Authors: Francesca Nardi, Kashish Aneja, Katherine Ginsbach
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The COVID-19 pandemic has demonstrated both a need for evidence-based and rights-based public health policy and how challenging it can be to make effective decisions with limited information, evidence, and data. The O’Neill Institute, in conjunction with several partners, has been working since the beginning of the pandemic to collect, analyze, and distribute critical data on public health policies enacted in response to COVID-19 around the world in the COVID-19 Law Lab. Well-designed laws and policies can help build strong health systems, implement necessary measures to combat viral transmission, enforce actions that promote public health and safety for everyone, and on the individual level have a direct impact on health outcomes. Poorly designed laws and policies, on the other hand, can fail to achieve the intended results and/or obstruct the realization of fundamental human rights, further disease spread, or cause unintended collateral harms. When done properly, laws can provide the foundation that brings clarity to complexity, embrace nuance, and identifies gaps of uncertainty. However, laws can also shape the societal factors that make disease possible. Law is inseparable from the rest of society, and COVID-19 has exposed just how much laws and policies intersects all facets of society. In the COVID-19 context, evidence-based and well-informed law and policy decisions—made at the right time and in the right place—can and have meant the difference between life or death for many. Having a solid evidentiary base of legal information can promote the understanding of what works well and where, and it can drive resources and action to where they are needed most. We know that legal mechanisms can enable nations to reduce inequities and prepare for emerging threats, like novel pathogens that result in deadly disease outbreaks or antibiotic resistance. The collection and analysis of data on these legal mechanisms is a critical step towards ensuring that legal interventions and legal landscapes are effectively incorporated into more traditional kinds of health science data analyses. The COVID-19 Law Labs see a unique opportunity to collect and analyze this kind of non-traditional data to inform policy using laws and policies from across the globe and across diseases. This global view is critical to assessing the efficacy of policies in a wide range of cultural, economic, and demographic circumstances. The COVID-19 Law Lab is not just a collection of legal texts relating to COVID-19; it is a dataset of concise and actionable legal information that can be used by health researchers, social scientists, academics, human rights advocates, law and policymakers, government decision-makers, and others for cross-disciplinary quantitative and qualitative analysis to identify best practices from this outbreak, and previous ones, to be better prepared for potential future public health events.Keywords: public health law, surveillance, policy, legal, data
Procedia PDF Downloads 141219 Pediatric Drug Resistance Tuberculosis Pattern, Side Effect Profile and Treatment Outcome: North India Experience
Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant
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Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment
Procedia PDF Downloads 66218 Toward Understanding the Glucocorticoid Receptor Network in Cancer
Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden
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The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor
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