Search results for: survival copula

Authors: Fentie, Belay, Mulat

Abstract:

In today’s high decrement figure of the global economy, nations are facing many economic, social and political challenges; universally, there is high distress of food and other survival insecurity. Further, as a result of conflict, natural disasters, and leadership influences, youths are existentially less empowered and unemployed, especially in developing countries. With this situation to handle well challenges, it’s important to search, investigate and deliberate about youth, unemployment, empowerment and possible management fashions, as youths have the potential to carry and fight such battles. The method adopted is a qualitative analysis of secondary data sources in youth empowerment, unemployment and development as an inclusive framework. Youth unemployment is a major development headache for most African countries. In Ethiopia, following weak youth empowerment, youth unemployment has increased from time to time, and quality education and organization linkage matter as an important constraint. As a management challenge, although accessibility of quality education for Ethiopian youths is an important constraint, the country's youths are fortified deceptively and harassed in a vicious political challenge in their struggle to fetch social and economic changes in the country. Further, thousands of youths are inactivated, criminalized and lost their lives and this makes youths hopeless anger in their lives and pushes them further to be exposed for addictions, prostitution, violence, and illegitimate migrations. This youth challenge wasn’t only destined for African countries; rather, indeed, it was a global burden and headed as a global agenda. As a resolution, the construction of a healthy education system can create independent youths who acquire success and accelerate development. Developing countries should ensue development in the cultivation of empowerment tools through long and short-term education, implementing policy in action, diminishing wide-ranging gaps of (religion, ethnicity & region), and take high youth population as an opportunity and empower them. Further managing and empowering youths to be involved in decision-making, giving political weight and building a network of organizations to easily access job opportunities are important suggestions to save youths in work, for both increasing their income and the country's food security balance.

Keywords: development, Ethiopia, management, unemployment, youth empowerment

Procedia PDF Downloads 57

Authors: Yui Okuno, Mariko Era, Takayoshi Kawahara, Takahide Kanyama, Hiroshi Morita

Abstract:

Introduction: Fungus and mite are known as allergens that cause an allergic disease for example asthma bronchiale and allergic rhinitis. Cladosporium cladosporioides is one of the most often detected fungi in the indoor environment and causes pollution and deterioration. Dermatophagoides farinae is major mite allergens indoors. Therefore, the creation of antifungal agents with high safety and the antifungal effect is required. Fatty acid salts are known that have antibacterial activities. This report describes the effects of fatty acid salts against Cladosporium cladosporioides NBRC 30314 and Dermatophagoides farinae. Methods: Potassium salts of 9 fatty acids (C4:0, C6:0, C8:0, C10:0, C12:0, C14:0, C18:1, C18:2, C18:3) were prepared by mixing the fatty acid with the appropriate amount of KOH solution to a concentration of 175 mM and pH 10.5. The antifungal method, the spore suspension (3.0×104 spores/mL) was mixed with a sample of fatty acid potassium (final concentration of 175 mM). Samples were counted at 0, 10, 60, 180 min by plating (100 µL) on PDA. Fungal colonies were counted after incubation for 3 days at 30 °C. The MIC (minimum inhibitory concentration) against the fungi was determined by the two-fold dilution method. Each fatty acid salts were inoculated separately with 400 µL of C. cladosporioides at 3.0 × 104 spores/mL. The mixtures were incubated at the respective temperature for each organism for 10 min. The tubes were then contacted with the fungi incubated at 30 °C for 7 days and examined for growth of spores on PDA. The acaricidal method, twenty D. farinae adult females were used and each adult was covered completely with 2 µL fatty acid potassium for 1 min. The adults were then dried with filter paper. The filter paper was folded and fixed by two clips and kept at 25 °C and 64 % RH. Mortalities were determained 48 h after treatment under the microscope. D. farina was considered to be dead if appendages did not move when prodded with a pin. Results and Conclusions: The results show that C8K, C10K, C12K, C14K was effective to decrease survival rate (4 log unit) of the fatty acids potassium incubated time for 10 min against C. cladosporioides. C18:3K was effective to decrease 4 log unit of the fatty acids potassium incubated time for 60 min. Especially, C12K was the highest antifungal activity and the MIC of C12K was 0.7 mM. On the other hand, the fatty acids potassium showed no acaricidal effects against D. farinae. The activity of D. farinae was not adversely affected after 48 hours. These results indicate that C12K has high antifungal activity against C. cladosporioides and suggest the fatty acid potassium will be used as an antifungal agent.

Keywords: fatty acid salts, antifungal effects, acaricidal effects, Cladosporium cladosporioides, Dermatophagoides farinae

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Authors: Mohammadjavad Sotoudeheian

Abstract:

COVID-19, which began in December 2019, uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter and spread through the cells. ACE2 mRNA is present in almost every organ, including nasopharynx, lung, as well as the brain. Ports of entry of SARS-CoV-2 into the central nervous system (CNS) may include arterial circulation, while viremia is remarkable. However, it is imperious to develop neurological symptoms evaluation CSF analysis in patients with COVID-19, but theoretically, ACE2 receptors are expressed in cerebellar cells and may be a target for SARS-CoV-2 infection in the brain. Recent evidence agrees that SARS-CoV-2 can impact the brain through direct and indirect injury. Two biomarkers for CNS injury, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL) detected in the plasma of patients with COVID-19. NFL, an axonal protein expressed in neurons, is related to axonal neurodegeneration, and GFAP is over-expressed in CNS inflammation. GFAP cytoplasmic accumulation causes Schwan cells to misfunction, so affects myelin generation, reduces neuroskeletal support over NfLs during CNS inflammation, and leads to axonal degeneration. Interleukin-6 (IL-6), which extensively over-express due to interleukin storm during COVID-19 inflammation, regulates gene expression, as well as GFAP through STAT molecular pathway. IL-6 also impresses the phosphoinositide 3-kinase (PI3K)/STAT/smads pathway. The PI3K/ protein kinase B (Akt) pathway is the main modulator upstream of the mammalian target of rapamycin (mTOR), and alterations in this pathway are common in neurodegenerative diseases. Most neurodegenerative diseases show a disruption of autophagic function and display an abnormal increase in protein aggregation that promotes cellular death. Therefore, induction of autophagy has been recommended as a rational approach to help neurons clear abnormal protein aggregates and survive. The mTOR is a major regulator of the autophagic process and is regulated by cellular stressors. The mTORC1 pathway and mTORC2, as complementary and important elements in mTORC1 signaling, have become relevant in the regulation of the autophagic process and cellular survival through the extracellular signal-regulated kinase (ERK) pathway.

Keywords: mTORC1, COVID-19, PI3K, autophagy, neurodegeneration

Procedia PDF Downloads 85

Authors: Mandy Wilson, Emma Vieira, Jocelyn Jones, Alice V. Brown, Lindey Andrews, Louise Southalan, Jackie Oakley, Dorothy Bagshaw, Patrick Egan, Laura Dent, Duc Dau, Lucy Spanswick

Abstract:

Alcohol and drug dependency are pertinent issues for those experiencing homelessness. This includes Aboriginal and Torres Strait Islander people, Australia’s traditional owners, living in Perth, Western Australia (WA). Societal narratives around the drivers behind drug and alcohol dependency in Aboriginal communities, particularly those experiencing homelessness, have been biased and unchanging, with little regard for complexity. This can include the idea that Aboriginal people have ‘chosen’ to use alcohol or other drugs without consideration for intergenerational trauma and the trauma of homelessness that may influence their choices. These narratives have flow-on impacts on policies and services that directly impact Aboriginal people experiencing homelessness. In 2021, we commenced a project which aimed to listen to and elevate the voices of 70-90 Aboriginal people experiencing homelessness in Perth. The project is community-driven, led by an Aboriginal Community Controlled Organisation in partnership with a university research institute. A community-ownership group of Aboriginal Elders endorsed the project’s methods, chosen to ensure their suitability for the Aboriginal community. In this paper, we detail these methods, including semi-structured interviews influenced by an Aboriginal yarning approach – an important style of conversation for Aboriginal people which follows cultural protocols; and photovoice – supporting people to share their stories through photography. Through these engagements, we detail the reasons Aboriginal people in Perth shared for using alcohol or other drugs while experiencing homelessness. These included supporting their survival on the streets, managing their mental health, and coping while on the journey to finding support. We also detail why they sought to discontinue alcohol and other drug use, including wanting to reconnect with family and changing priorities. Finally, we share how Aboriginal people experiencing homelessness have said they are impacted by their family’s alcohol and other drug use, including feeling uncomfortable living with a family who is drug and alcohol-dependent and having to care for grandchildren despite their own homelessness. These findings provide a richer understanding of alcohol and drug use for Aboriginal people experiencing homelessness in Perth, shedding light on potential changes to targeted policy and service approaches.

Keywords: Aboriginal and Torres Strait Islander peoples, alcohol and other drugs, homelessness, community-led research

Procedia PDF Downloads 129

Authors: Maria L. G. Lourenco, Keylla H. N. P. Pereira, Viviane Y. Hibaru, Fabiana F. Souza, Joao C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

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Neonatal sepsis is a systemic response of acute infection by bacteria that may lead to high mortality in a litter. This study aims to report a case of sepsis by alpha-hemolytic Streptococcus and Mannheimia haemolytica in neonate dogs. A pregnant, mixed-breed bitch at approximately the 60th day of pregnancy was admitted to the Sao Paulo State University (UNESP) Veterinary Hospital, Botucatu, Sao Paulo, Brazil, and subjected to a c-section due to uterine atony and fetuses no heartbeats on the ultrasound examination. The mother presented leukopenia of 1.6 thousand leukocytes, and there was no other information regarding previous clinical history. Among the offspring, four were stillborn, and five were born alive. On clinical examination, neonates weighed between 312 and 384 grams. Reflexes were present, and the newborn's body temperature was between 89.9 ºF and 96.4 ºF. Neonates also presented clinical signs of neonatal infection: omphalitis, abdomen, and extremities with cyanotic color, hematuria, and diarrhea (meconium). Complementary tests revealed leukopenia. The presence of alpha hemolytic streptococcus and Mannheimia haemolytica was revealed in the bacterial culture. The bacteria were sensitive to cephalosporins and penicillin on the antibiogram. Treatment for sepsis was instituted with the drug ceftriaxone, at a dose of 50 mg per kilogram, administered intravenous (jugular vein). Subsequently administered subcutaneous, every 12 hours, for seven days. Heated fluid therapy was performed, with Ringer lactate, at a dose of 4 ml per 100 grams of weight, intravenous. Heating measures were instituted. Blood plasma was also administered, at a dose of 2 mL per 100 grams of weight, administered subcutaneous, as a source of passive immunity. A maternal milk substitute was instituted, and lactation was discontinued since the mother was unable to nurse due to the infection. The mother was neutered during the c-section and treated with ceftriaxone (50 mg/kg). After seven days, the newborns presented normal clinical signs and no alterations in the hemogram. Early diagnosis and intervention were essential for the survival of these patients.

Keywords: neonatal infection, puppies, bacteria, newborn

Procedia PDF Downloads 120

Authors: Lubaina Soni, Claire Farrell, Christopher Szota, Tim D. Fletcher

Abstract:

Green roofs are a promising engineered ecosystem for reducing stormwater runoff and restoring vegetation cover in cities. Plants can contribute to rainfall retention by rapidly depleting water in the substrate; however, this increases the risk of plant drought stress. Green roof configurations, therefore, need to provide plants the opportunity to efficiently deplete the substrate but also avoid severe drought stress. This study used green roof modules placed in a rainout shelter during a six-month rainfall regime simulated in Melbourne, Australia. Rainfall was applied equally with an overhead irrigation system on each module. Aside from rainfall, modules were under natural climatic conditions, including temperature, wind, and radiation. A single species, Ficinia nodosa, was planted with five different treatments and three replicates of each treatment. In this experiment, we tested the impact of three plant cover treatments (0%, 50% and 100%) on rainfall retention and plant drought stress. We also installed two runoff zone treatments covering 50% of the substrate surface for additional modules with 0% and 50% plant cover to determine whether directing rainfall resources towards plant roots would reduce drought stress without impacting rainfall retention. The retention performance for the simulated rainfall events was measured, quantifying all components for hydrological performance and survival on green roofs. We found that evapotranspiration and rainfall retention were similar for modules with 50% and 100% plant cover. However, modules with 100% plant cover showed significantly higher plant drought stress. Therefore, planting at a lower cover/density reduced plant drought stress without jeopardizing rainfall retention performance. Installing runoff zones marginally reduced evapotranspiration and rainfall retention, but by approximately the same amount for modules with 0% and 50% plant cover. This indicates that reduced evaporation due to the installation of the runoff zones likely contributed to reduced evapotranspiration and rainfall retention. Further, runoff occurred from modules with runoff zones faster than those without, indicating that we created a faster pathway for water to enter and leave the substrate, which also likely contributed to lower overall evapotranspiration and retention. However, despite some loss in retention performance, modules with 50% plant cover installed with runoff zones showed significantly lower drought stress in plants compared to those without runoff zones. Overall, we suggest that reducing plant cover represents a simple means of optimizing green roof performance but creating runoff zones may reduce plant drought stress at the cost of reduced rainfall retention.

Keywords: green roof, plant cover, plant drought stress, rainfall retention

Procedia PDF Downloads 115

Authors: Jacques M. Berner, Monja Gerber, Gillian L. Maggs-Kolling, Stuart J. Piketh

Abstract:

The enigmatic melon species, Acanthosicyos horridus Welw. ex Hook. f., locally known as !nara, is endemic to the hyper-arid Namib Desert, where it thrives in sandy dune areas and dry river banks. The Namib Desert is characterized by extreme weather conditions which include high temperatures, very low rainfall, and extremely dry air. Plant and animals that have made the Namib Dessert their home are dependent on non-rainfall water inputs, like fog, dew and water vapor, for survival. Fog is believed to be the most important non-rainfall water input for most of the coastal Namib Desert and is a life line to many Namib plants and animals. It is commonly assumed that the !nara plant is adapted and dependent upon coastal fog events. The !nara plant shares many comparable adaptive features with other organisms that are known to exploit fog as a source of moisture. These include groove-like structures on the stems and the cone-like structures of thorns. These structures are believed to be the driving forces behind directional water flow that allow plants to take advantage of fog events. The !nara-fog interaction was investigated in this study to determine the dependence of !nara on these fog events, as it would illustrate strategies to benefit from non-rainfall water inputs. The direct water uptake capacity of !nara shoots was investigated through absorption tests. Furthermore, the movement and behavior of fluorescent water droplets on a !nara stem were investigated through time-lapse macrophotography. The shoot water potential was measured to investigate the effect of fog on the water status of !nara stems. These tests were used to determine whether the morphology of !nara has evolved to exploit fog as a non-rainfall water input and whether the !nara plant has adapted physiologically in response to fog. Chlorophyll a fluorescence was used to compare the photochemical efficiency of !nara plants on days with fog events to that on non-foggy days. The results indicate that !nara plants do have the ability to take advantage of fog events as commonly believed. However, the !nara plant did not exhibit visible signs of drought stress and this, together with the strong shoot water potential, indicates that these plants are reliant on permanent underground water sources. Chlorophyll a fluorescence data indicated that temperature stress and wind were some of the main abiotic factors influencing the plants’ overall vitality.

Keywords: Acanthosicyos horridus, chlorophyll a fluorescence, fog, foliar absorption, !nara

Procedia PDF Downloads 157

Authors: Belay Mulat Fentie

Abstract:

In today’s high decrement figure of the global economy, nations are facing many economic, social, and political challenges; universally, there is high distress of food and other survival insecurity. Further, as a result of conflict, natural disaster, and leadership influences, youths are existentially less empowered and unemployed, especially in developing countries. With this situation to handle well challenges, it’s important to search, investigate and deliberate about youth, unemployment, empowerment, and possible management fashions, as youths has a potential to carry and fight such battles. The method adopted is qualitative analysis of secondary data sources in youth empowerment, unemployment, and development as inclusive framework. Youth unemployment is a major development headache for most African countries. In Ethiopia, following weak youth empowerment, youth unemployment has been increased time to time; and quality education and organizations linkage matters as an important constraint. As a management challenge, although accessibility of quality education for Ethiopian youths is an important constraint; the country youths fortified deceptively and harassed in a vicious political challenge in their struggle to fetch social and economic changes in the country. Further, thousands of youths inactivated, criminalized, and lost their lives, and this makes youths to be hopeless, anger in their lives and pushes further to expose for addictions, prostitution, violence, and illegitimate migrations. This youth challenge didn’t only destinate in African countries, rather, indeed, the global burden and headed as a global agenda. As a resolution, the construction of a healthy education system can create independent youths that acquire success and accelerate development. Developing countries should ensue development in cultivation of empowerment tool through long and short-term education, implementing policy in action, diminishing wide ranged gaps of (religion, ethnicity & region), and take the high youth population as an opportunity and empower them. And further manage and empower youths to involve in decision making, in giving political weight and build a network on organizations to easily access jobs opportunities are important suggestion to alive youths in work, for both increasing their income and country food security balance.

Keywords: development, Ethiopia, management, unemployment, youth empowerment

Procedia PDF Downloads 137

Authors: Ugo Rovigatti

Abstract:

Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

Procedia PDF Downloads 99

Authors: Osama Moustafa Zayed

Abstract:

Aim of the work: To evaluate the effectiveness of venous glucose, levels of serum lactate and base deficit in polytraumatized patients as simple parameters to predict the mortality in these patients. Compared to the predictive value of Trauma and injury severity (TRISS) and Acute Physiology And Chronic Health Evaluation IV (APACHE IV). Introduction: Trauma is a serious global health problem, accounting for approximately one in 10 deaths worldwide. Trauma accounts for 5 million deaths per year. Prediction of mortality in trauma patients is an important part of trauma care. Several trauma scores have been devised to predict injury severity and risk of mortality. The trauma and injury severity score (TRISS) was most common used. Regardless of the accuracy of trauma scores, is based on an anatomical description of every injury and cannot be assigned to the patients until a full diagnostic procedure has been performed. So we hypothesized that alterations in admission glucose, lactate levels and base deficit would be an early and easy rapid predictor of mortality. Patient and Method: a comparative cross-sectional study. 282 Polytraumatized patients attended to the Emergency Department(ED) of the Suez Canal university Hospital constituted. The period from 1/1/2012 to 1/4/2013 was included. Results: We found that the best cut off value of TRISS probability of survival score for prediction of mortality among poly-traumatized patients is = 90, with 77% sensitivity and 89% specificity using area under the ROC curve (0.89) at (95%CI). APACHE IV demonstrated 67% sensitivity and 95% specificity at 95% CI at cut off point 99. The best cutoff value of Random Blood Sugar (RBS) for prediction of mortality was>140 mg/dl, with 89%, sensitivity, 49% specificity. The best cut off value of base deficit for prediction of mortality was less than -5.6 with 64% sensitivity, 93% specificity. The best cutoff point of lactate for prediction of mortality was > 2.6 mmol/L with 92%, sensitivity, 42% specificity. Conclusion: According to our results from all evaluated predictors of mortality (laboratory and scores) and mortality based on the estimated cutoff values using ROC curves analysis, the highest risk of mortality was found using a cutoff value of 90 in TRISS score while with laboratory parameters the highest risk of mortality was with serum lactate > 2.6 . Although that all of the three parameter are accurate in predicting mortality in poly-traumatized patients and near with each other, as in serum lactate the area under the curve 0.82, in BD 0.79 and 0.77 in RBS.

Keywords: APACHE IV, emergency department, polytraumatized patients, serum lactate

Procedia PDF Downloads 292

Authors: L. Hoade, O. O. Onafowokan, K. Anderson, G. E. Bartlett, E. D. Fern, M. R. Norton, R. G. Middleton

Abstract:

Aims: Femoroacetabular impingement (FAI) was first recognised as a potential driver for hip pain at the turn of the last millennium. While there is an increasing trend towards surgical management of FAI by arthroscopic means, open surgical hip dislocation and debridement (SHD) remains the Gold Standard of care in terms of reported outcome measures. (1) Long-term functional and survivorship outcomes of SHD as a treatment for FAI are yet to be sufficiently reported in the literature. This study sets out to help address this imbalance. Methods: We undertook a retrospective review of our institutional database for all patients who underwent SHD for FAI between January 2003 and December 2008. A total of 223 patients (241 hips) were identified and underwent a ten year review with a standardised radiograph and patient-reported outcome measures questionnaire. The primary outcome measure of interest was survivorship, defined as progression to total hip arthroplasty (THA). Negative predictive factors were analysed. Secondary outcome measures of interest were survivorship to further (non-arthroplasty) surgery, functional outcomes as reflected by patient reported outcome measure scores (PROMS) scores, and whether a learning curve could be identified. Results: The final cohort consisted of 131 females and 110 males, with a mean age of 34 years. There was an overall native hip joint survival rate of 85.4% at ten years. Those who underwent a THA were significantly older at initial surgery, had radiographic evidence of preoperative osteoarthritis and pre- and post-operative acetabular undercoverage. In those whom had not progressed to THA, the average Non-arthritic Hip Score and Oxford Hip Score at ten year follow-up were 72.3% and 36/48, respectively, and 84% still deemed their surgery worthwhile. A learning curve was found to exist that was predicated on case selection rather than surgical technique. Conclusion: This is only the second study to evaluate the long-term outcomes (beyond ten years) of SHD for FAI and the first outside the originating centre. Our results suggest that, with correct patient selection, this remains an operation with worthwhile outcomes at ten years. How the results of open surgery compared to those of arthroscopy remains to be answered. While these results precede the advent of collison software modelling tools, this data helps set a benchmark for future comparison of other techniques effectiveness at the ten year mark.

Keywords: femoroacetabular impingement, hip pain, surgical hip dislocation, hip debridement

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Authors: Martina Santobuono, Wing Sze Chan, Elettra D'Amico, Henriette Selck

Abstract:

Chemicals in modern society are fundamental in many different aspects of daily human life. We use a wide range of substances, including polychlorinated compounds, pesticides, plasticizers, and pharmaceuticals, to name a few. These compounds are excessively produced, and this has led to their introduction to the environment and food resources. Municipal and industrial effluents, landfills, and agricultural runoffs are a few examples of sources of chemical pollution. Many of these compounds, such as pharmaceuticals, have been proven to mimic or alter the performance of the hormone system, thus disrupting its normal function and altering the behavior and reproductive capability of non-target organisms. Antidepressants are pharmaceuticals commonly detected in the environment, usually in the range of ng L⁻¹ and µg L⁻¹. Since they are designed to have a biological effect at low concentrations, they might pose a risk to the native species, especially if exposure lasts for long periods. Hydrophobic antidepressants, like the selective serotonin reuptake inhibitor (SSRI) Sertraline, can sorb to the particles in the water column and eventually accumulate in the sediment compartment. Thus, deposit-feeding organisms may be at particular risk of exposure. The polychaete Capitella teleta is widespread in estuarine organically enriched sediments, being a key deposit-feeder involved in geochemistry processes happening in sediments. Since antidepressants are neurotoxic chemicals and endocrine disruptors, the aim of this work was to test if sediment-associated Sertraline impacts burrowing- and feeding behavior as well as reproduction capability in Capitella teleta in a chronic exposure set-up, which could better mimic what happens in the environment. 7 days old juveniles were selected and exposed to different concentrations of Sertraline for an entire generation until the mature stage was reached. This work was able to show that some concentrations of Sertraline altered growth and the time of first reproduction in Capitella teleta juveniles, potentially disrupting the population’s capability of survival. Acknowledgments: This Ph.D. position is part of the CHRONIC project “Chronic exposure scenarios driving environmental risks of Chemicals”, which is an Innovative Training Network (ITN) funded by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Actions (MSCA).

Keywords: antidepressants, Capitella teleta, chronic exposure, endocrine disruption, sublethal endpoints, neurotoxicity

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Authors: Elzbieta Sikorska-Simmons

Abstract:

Dementia is a progressive terminal disease. Despite this recognition, research shows that most family caregivers do not know it, and it is unclear how this knowledge affects the quality of patient care. The aim of this qualitative study of 20 family caregivers for patients with advanced dementia is to examine how the caregiver's knowledge about dementia affects the quality of patient care in the context of healthcare decision-making, advanced care planning, and access to adequate support systems. Knowledge about dementia implies family caregivers' understanding of dementia trajectories, common symptoms/complications, and alternative treatment options (e.g., comfort feeding versus tube feeding). Data were collected in semi-structured interviews with 20 family caregivers. The interviews were conducted in person by the author and designed to elicit rich descriptions of family caregivers' experiences with healthcare decision-making and the management of common symptoms/complications of end-stage dementia as patient healthcare proxies. The study findings suggest that caregivers who recognize that dementia is a terminal disease are less likely to opt for life-extending treatments during the advanced stages. They are also more likely to seek palliative/hospice care, and consequently, they are better able to avoid unnecessary hospitalizations or medical procedures. For example, those who know that dementia is a terminal disease tend to opt for "comfort feeding" rather than "tube feeding" in managing the swallowing difficulties that accompany advanced dementia. In the context of advance care planning, family caregivers who know that dementia is a terminal disease tend to have more meaningful advance directives (e.g., Power of Attorney and Do Not Resuscitate orders). They are better prepared to anticipate common problems and pursue treatments that foster the best quality of patient life and care. Greater knowledge about advanced dementia helps them make more informed decisions that focus on enhancing the quality of patient life rather than just survival. In addition, those who know that dementia is a terminal disease are more likely to establish adequate support systems to help them cope with the complex demands of caregiving. For example, they are more likely to seek dementia-oriented primary care programs that offer house visits or respite services. Based on the study findings, knowledge about dementia as a terminal disease is critical in the optimal management of patient care needs and the establishment of adequate support systems. More research is needed to better understand what caregivers need to know to better prepare them for the complex demands of dementia caregiving.

Keywords: dementia education, family caregiver, management of dementia, quality of care

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Authors: Arpit Gite

Abstract:

Purpose: We have evaluated the role of Total Neoadjuvant Therapy in patients with Locally Advanced Rectal cancer by giving Chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and, after that, the strategy of wait and watch. Methods: In this prospective case series, we evaluated the results of three locally advanced Rectal cancers, two cases Stage II (cT3N0) and one case Stage III ( cT4aN2). All three patients' growth was 4-6 cm from the anal verge. We have treated with Chemoradiotherapy to dose of 45Gy/25 Fractions to elective nodal regions (Inguinal node in anal canal Involvement)and Primary and mesorectum (Phase I) followed by 14.4Gy/8 Fractions to Primary and Mesorectum(Phase II) to a total dose of 59.4Gy/33 Fractions with concurrent chemotherapy Tab Capecitabine 825mg/m2 PO BD with Radiation therapy. After 6 weeks of completion of Chemoradiotherapy, advised six cycles of consolidative chemotherapy, CAPEOX regimen, Oxaliplatin 130mg/m2 on day 1 and Capecitabine 1000mg/m2 PO BD on days 1-14 repeated on a 21-day cycle for a total of six cycles. The primary endpoint is Disease-free survival (DFS); the secondary endpoint is adverse events related to chemoradiotherapy. Radiation toxicity is assessed by RTOG criteria, and chemotherapy toxicity is assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: After 6 weeks of completion of Chemoradiotherapy, we did PET-CT of all three patients; all three patients had a clinically complete response and we advised 6 cycles of consolidative chemotherapy. After completion of consolidative chemotherapy, again PET-CT and sigmoidoscopy, all three patients had complete response on PET-CT and no lesions on sigmoidoscopy and kept all three patients on wait and watch.2 patients had Grade 2 skin toxicities,1 patient had Grade 1 skin toxicity, .2 patients had Grade 2 lower GI toxicities, and 1 patient had Grade lower GI toxicity, both according to RTOG criteria. 3 patients had Grade 2 diarrhea due to capecitabine, and 1 patient had Grade 1 thrombocytopenia due to oxaliplatin assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Conclusion: Sphincter Preservation is possible with this regimen in those who don’t want to opt for surgery or in case of low-lying rectal cancer.

Keywords: locally advanced rectal cancer, sphincter preservation, chemoradiotherapy, consolidative chemotherapy

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Authors: Marin Kanarev, Delyan Stoyanov, Ivanna Popova, Nadezhda Petrova

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Thanks to increased survival rates in patients bearing oncological malignancies due to recent developments in anti-cancer therapies and diagnostic techniques, observation of clinical cases of metachronous cancers is more common and can provide more in-depth knowledge of their development and, as a result, help clinicians apply suitable therapy. This unusual case of three metachronous tumors presented the opportunity to follow their occurrence, progression, and treatment thoroughly. A 77-year-old male presented with carcinoma ventriculi of the pylorus region, which was surgically removed via upper subtotal stomach resection, a lateral antecolical gastro-enteroanastomosis, and a subsequent Braun anastomosis. An EOX chemotherapy regimen followed. A CT scan four months later showed no indication of recurrence or dissemination. The same scan, performed as a part of the follow-up plan two years later, showed an indication of neoplastic growth in the urinary bladder. After the patient had been directed to a urologist, the suspicion was confirmed, and the growth was histologically diagnosed as a carcinoma of the urinary bladder. An immunohistochemistry test showed an expression of PDL1 of less than 5%, which resulted in treatment with GemCis chemotherapy regimen that led to full remission. Two years and seven months after the first surgery, a CT scan showed again that the two carcinomas were gone. However, four months later, elevated tumor markers prompted a PET/CT scan, which showed data indicative of recurring neoplastic growth in the region of the stomach cardia. It was diagnosed as an adenocarcinoma infiltrating the esophagus. Preoperative chemotherapy with the ECF regimen was completed in four courses, and a CT scan showed no progression of the disease. In less than a month after therapy, the patient underwent laparotomy, debridement, gastrectomy, and a subsequent mechanical terminal-lateral esophago-jejunoanasthomosis. It was verified that the tumor originated from metastasis from the carcinoma ventriculi, which was located in the pylorus. In conclusion, this case report highlights the importance of patient follow-up and studying recurring neoplastic growth. Despite the absence of symptoms, clinicians should maintain a high level of suspicion when evaluating the patient data and choosing the most suitable therapy.

Keywords: carcinoma, follow-up, metachronous, neoplastic growth, recurrence

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Authors: Marco Camilli

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This article examines the impact of the pandemic outbreak of COVID-19 in the tourism sector in Italy, analyzing the current scenario, the government decisions and the private company reaction for the summer season 2020. The framework of the data analyzed shows how massive it’s the impact of the pandemic outbreak in the tourism revenue, and the weaknesses of the measures proposed. Keywords Travel &Tourism, Transportation, Sustainability, COVID-19, Businesses Introduction The current COVID-19 scenario shows a shocking situation for the tourism and transportation sectors: it could be the most affected by the Coronavirus in Italy. According to forecasts, depending on the duration of the epidemic outbreak and the lockdown strategy applied by the Government, businesses in the supply chain could lose between 24 and 66 billion in turnover in the period of 2020-21, with huge diversified impacts at the national and regional level. Many tourist companies are on the verge of survival and if there are no massive measures by the government they risk closure. Data analysis The tourism and transport sector could be among the sectors most damaged by Covid-19 in Italy. Considering the two-year period 2020-21, companies operating in the travel & tourism sector (Tour operator, Travel Agencies, Hotel, Guides, Bus Company, etc..) could in suffer losses in revenues of 24 to 64 billion euros, especially in the sectors such as the travel agencies, hotel and rental. According to Statista Research Department, from April 2020 estimated that the coronavirus (COVID-19) pandemic will have a significant impact on revenues of the tourism industry in Italy. Revenues are expected to decrease by over 40 billion euros in the first semester of 2020, compared to the same period of the previous year. According to the study, hotel and non-hotel accommodations will experience the highest loss. Revenues of this sector are expected to decrease by 13 billion euros compared to the first semester of 2019 when accommodations registered revenues for about 17 billion euros. According to Statista.com, in 2020, Italy is expected to register a decrease of roughly 28.5 million tourist arrivals due to the impact of coronavirus (COVID-19) on the country's tourist sector. According to the estimate, the region of Veneto will record the highest drop with a decrease of roughly 4.61 million arrivals. Similarly, Lombardy is expected to register a decrease of about 3.87 million arrivals in 2020.

Keywords: travel and tourism, sustainability, COVID-19, businesses, transportation

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Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

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T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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Authors: Kangana Sengar, Sanjay Deb, Ramesh Dawar

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Introduction: Ki-67 can be a useful marker in determining proliferative activity in patients with multiple myeloma (MM). However, using Ki-67 alone results in the erroneous inclusion of non-myeloma cells leading to false high counts. We have used Dual IHC (immunohistochemistry) staining with Ki-67 and CD138 to enhance specificity in assessing proliferative activity of bone marrow plasma cells. Aims and objectives: To estimate the proportion of proliferating (Ki-67 expressing) plasma cells in patients with MM and correlation of Ki-67 with other known prognostic parameters. Materials and Methods: Fifty FFPE (formalin fixed paraffin embedded) blocks of trephine biopsies of cases diagnosed as MM from 2010 to 2015 are subjected to H & E staining and Dual IHC staining for CD 138 and Ki-67. H & E staining is done to evaluate various histological parameters like percentage of plasma cells, pattern of infiltration (nodular, interstitial, mixed and diffuse), routine parameters of marrow cellularity and hematopoiesis. Clinical data is collected from patient records from Medical Record Department. Each of CD138 expressing cells (cytoplasmic, red) are scored as proliferating plasma cells (containing a brown Ki¬67 nucleus) or non¬proliferating plasma cells (containing a blue, counter-stained, Ki-¬67 negative nucleus). Ki-67 is measured as percentage positivity with a maximum score of hundred percent and lowest of zero percent. The intensity of staining is not relevant. Results: Statistically significant correlation of Ki-67 in D-S Stage (Durie & Salmon Stage) I vs. III (p=0.026) and ISS (International Staging System) Stage I vs. III (p=0.019), β2m (p=0.029) and percentage of plasma cells (p < 0.001) is seen. No statistically significant correlation is seen between Ki-67 and hemoglobin, platelet count, total leukocyte count, total protein, albumin, S. calcium, S. creatinine, S. LDH, blood urea and pattern of infiltration. Conclusion: Ki-67 index correlated with other known prognostic parameters. However, it is not determined routinely in patients with MM due to little information available regarding its relevance and paucity of studies done to correlate with other known prognostic factors in MM patients. To the best of our knowledge, this is the first study in India using Dual IHC staining for Ki-67 and CD138 in MM patients. Routine determination of Ki-67 will help to identify patients who may benefit with more aggressive therapy. Recommendation: In this study follow up of patients is not included, and the sample size is small. Studying with larger sample size and long follow up is advocated to prognosticate Ki-67 as a marker of survival in patients with multiple myeloma.

Keywords: bone marrow, dual IHC, Ki-67, multiple myeloma

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Authors: Marcio Freire Cruz, Naoaki Ono, Shigehiko Kanaya, Carlos Arthur Mattos Teixeira Cavalcante

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The systems that record patient care information, known as Electronic Medical Record (EMR) and those that monitor vital signs of patients, such as heart rate, body temperature, and blood pressure have been extremely valuable for the effectiveness of the patient’s treatment. Several kinds of research have been using data from EMRs and vital signs of patients to predict illnesses. Among them, we highlight those that intend to predict, classify, or, at least identify patterns, of sepsis illness in patients under vital signs monitoring. Sepsis is an organic dysfunction caused by a dysregulated patient's response to an infection that affects millions of people worldwide. Early detection of sepsis is expected to provide a significant improvement in its treatment. Preceding works usually combined medical, statistical, mathematical and computational models to develop detection methods for early prediction, getting higher accuracies, and using the smallest number of variables. Among other techniques, we could find researches using survival analysis, specialist systems, machine learning and deep learning that reached great results. In our research, patients are modeled as points moving each hour in an n-dimensional space where n is the number of vital signs (variables). These points can reach a sepsis target point after some time. For now, the sepsis target point was calculated using the median of all patients’ variables on the sepsis onset. From these points, we calculate for each hour the position vector, the first derivative (velocity vector) and the second derivative (acceleration vector) of the variables to evaluate their behavior. And we construct a prediction model based on a Long Short-Term Memory (LSTM) Network, including these derivatives as explanatory variables. The accuracy of the prediction 6 hours before the time of sepsis, considering only the vital signs reached 83.24% and by including the vectors position, speed, and acceleration, we obtained 94.96%. The data are being collected from Medical Information Mart for Intensive Care (MIMIC) Database, a public database that contains vital signs, laboratory test results, observations, notes, and so on, from more than 60.000 patients.

Keywords: dynamic analysis, long short-term memory, prediction, sepsis

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Authors: Muzaffer Topgul, Hasan Atac

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In case of explaining the migration concept, although it is not a new phenomenon, it is easy to understand that communities have migrated for variety of reasons such as natural disasters, famine, wars, economic problems, and several theories have been put forth to define and find solution for migration within its changing nature. Examining of migration theories denotes that the circumstances under which they appear reflect political, social, and economic conditions of the age they appear. In this day and time, security is considered not only from military perspective but also from economic, political, sociological dimensions. Based on the changing security environment new impacts of migration has occurred; the migration is proceed to be conferred as a type of war, qualified as a transnational crime because of its outcomes and interpreted in a different dimension owing to its effects on the health and education areas. Social security dimension in the context of expanding concept of security; when dealing with the safety of people and social groups with the assumption that national unity and identity are threatened, it sees immigrants as a source of threat. The human security assesses the safety of individuals in terms of survival and quality of life. Changes in the standard of living under the influence of immigrants and possible terrorist acts can be seen as a threat source in this type of security. Economic security of the individuals and the regional changes at the micro level created by the immigrants are covered issues of economic security. Due to the factors such as terrorism and civil war, the increasing numbers of displaced people who have taken refugee status affect the countries, whether it is near or far to the crisis areas, in the new and different dimensions of security day by day. In this study, the term of immigration through the eyes of national and international law will be evaluated, the place of the irregular and illegal immigration in the changing security sphere will be revealed and the effects of the irregular migration to short-term, mid-term and long-term security issues will be assessed through human and social security aspects. In order to analyze the threats for the human security; the parameters such as living conditions of the immigrants, the ratio of the genders, birth rate occasions, the education circumstances of the immigrant children and the effects of the illegal passing on the public order will be evaluated. The outcomes of the problem areas for the human security and the demographic alteration resulting from the human flow of displaced people will be discussed thorough social security extent. The fizzling economic diversity, which has shown up by irregular migration, will be presented within the scope of economic dimension of security.

Keywords: irregular migration, the changing dimensions of security, human security, social security

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Authors: Astrid Tannert, Anuradha Ramoji, Christina Ebert, Frederike Gladigau, Lorena Tuchscherr, Jürgen Popp, Ute Neugebauer

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Staphylococcus aureus is a facultative intracellular pathogen, which by entering host cells may evade immunologic host response as well as antimicrobial treatment. In that way, S. aureus can cause persistent intracellular infections which are difficult to treat. Depending on the strain, S. aureus may persist at different intracellular locations like the phagolysosome. The first barrier invading pathogens from the blood stream that they have to cross are the endothelial cells lining the inner surface of blood and lymphatic vessels. Upon proceeding from an acute to a chronic infection, intracellular pathogens undergo certain biochemical and structural changes including a deceleration of metabolic processes to adopt for long-term intracellular survival and the development of a special phenotype designated as small colony variant. In this study, the endothelial cell line Ea.hy 926 was used as a model for acute and chronic S. aureus infection. To this end, Ea.hy 926 cells were cultured on QIAscout™ Microraft Arrays, a special graded cell culture substrate that contains around 12,000 microrafts of 200 µm edge length. After attachment to the substrate, the endothelial cells were infected with GFP-expressing S. aureus for 3 weeks. The acute infection and the development of persistent bacteria was followed by confocal laser scanning microscopy, scanning the whole Microraft Array for the presence and for detailed determination of the intracellular location of fluorescent intracellular bacteria every second day. After three weeks of infection representative microrafts containing infected cells, cells with protruded infections and cells that did never show any infection were isolated and fixed for Raman micro-spectroscopic investigation. For comparison, also microrafts with acute infection were isolated. The acquired Raman spectra are correlated with the fluorescence microscopic images to give hints about a) the molecular alterations in endothelial cells during acute and chronic infection compared to non-infected cells, and b) metabolic and structural changes within the pathogen when entering a mode of persistence within host cells. We thank Dr. Ruth Kläver from QIAGEN GmbH for her support regarding QIAscout technology. Financial support by the BMBF via the CSCC (FKZ 01EO1502) and from the DFG via the Jena Biophotonic and Imaging Laboratory (JBIL, FKZ PO 633/29-1, BA 1601/10-1) is highly acknowledged.

Keywords: correlative image analysis, intracellular infection, pathogen-host adaption, Raman micro-spectroscopy

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Authors: Deepak Jugran

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Purpose: The purpose of this study is to identify how past Pandemics shaped social evolution and cities. Methodology: A historical and comparative analysis of major historical pandemics in human history their origin, transmission route, biological response and the aftereffects. A Comprehensive pre & post pandemic scenario and focuses selectively on major issues and pandemics that have deepest & lasting impact on society with available secondary data. Results: Past pandemics shaped the behavior of human societies and their cities and made them more resilient biologically, intellectually & socially endorsing the theory of “Survival of the fittest” by Sir Charles Darwin. Pandemics & Infectious diseases are here to stay and as a human society, we need to strengthen our collective response & preparedness besides evolving mechanisms for strict controls on inter-continental movements of people, & especially animals who become carriers for these viruses. Conclusion: Pandemics always resulted in great mortality, but they also improved the overall individual human immunology & collective social response; at the same time, they also improved the public health system of cities, health delivery systems, water, sewage distribution system, institutionalized various welfare reforms and overall collective social response by the societies. It made human beings more resilient biologically, intellectually, and socially hence endorsing the theory of “AGIL” by Prof Talcott Parsons. Pandemics & infectious diseases are here to stay and as humans, we need to strengthen our city response & preparedness besides evolving mechanisms for strict controls on inter-continental movements of people, especially animals who always acted as carriers for these novel viruses. Pandemics over the years acted like natural storms, mitigated the prevailing social imbalances and laid the foundation for scientific discoveries. We understand that post-Covid-19, institutionalized city, state and national mechanisms will get strengthened and the recommendations issued by the various expert groups which were ignored earlier will now be implemented for reliable anticipation, better preparedness & help to minimize the impact of Pandemics. Our analysis does not intend to present chronological findings of pandemics but rather focuses selectively on major pandemics in history, their causes and how they wiped out an entire city’s population and influenced the societies, their behavior and facilitated social evolution.

Keywords: pandemics, Covid-19, social evolution, cities

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Authors: Teklay Gebrecherkos, Mahmud Abdulkadir

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Abstract: The emergence and subsequent rapid worldwide spread of the COVID-19 pandemic have posed a global crisis, with a tremendously increasing burden of infection, morbidity, and mortality risks. Recent studies have suggested that severe cases of COVID-19 are characterized by massive biochemical, hematological, and inflammatory alterations whose synergistic effect is estimated to progress to multiple organ damage and failure. In this regard, biochemical monitoring of COVID-19 patients, based on comprehensive laboratory assessments and findings, is expected to play a crucial role in effective clinical management and improving the survival rates of patients. However, biochemical markers that can be informative of COVID-19 patient risk stratification and predictor of clinical outcomes are currently scarcely available. The study aims to investigate the profiles of common biochemical markers and their influence on the severity of the COVID-19 infection in Tigray, Ethiopia. Methods: A laboratory-based cross-sectional study was conducted from July to August 2020 at Quiha College of Engineering, Mekelle University COVID-19 isolation and treatment center. Sociodemographic and clinical data were collected using a structured questionnaire. Whole blood was collected from each study participant, and serum samples were separated after being delivered to the laboratory. Hematological biomarkers were analyzed using FACS count, while organ tests and serum electrolytes were analyzed using ion-selective electrode methods using a Cobas-6000 series machine. Data was analyzed using SPSS Vs 20. Results: A total of 120 SARS-CoV-2 patients were enrolled during the study. The participants ranged between 18 and 91 years, with a mean age of 52 (±108.8). The majority (40%) of participants were between the ages of 60 and above. Patients with multiple comorbidities developed severe COVID-19, though not statistically significant (p=0.34). Mann-Whitney U test analysis showed that biochemical tests such as neuropile count (p=0.003), AST levels (p=0.050), serum creatinine (p=0.000), and serum sodium (p=0.015) were significantly correlated with severe COVID-19 disease as compared to non-severe disease. Conclusion: The severity of COVID-19 was associated with higher age, organ tests AST and creatinine, serum Na+, and elevated total neutrophile count. Thus, further study needs to be conducted to evaluate the alterations of biochemical biomarkers and their impact on COVID-19.

Keywords: COVID-19, biomarkers, mortality, Tigray, Ethiopia

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Authors: Frans J. Smit, Wisdom A. Munzeiwa, Hermanus C. M. Vosloo, Lyn-Marie Birkholtz, Richard K. Haynes

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Malaria and antimicrobial infections remain significant global health concerns, necessitating the continuous search for novel therapeutic approaches. This abstract presents an overview of the potential use of triazenes as effective agents against malaria and various antimicrobial pathogens. Triazenes are a class of compounds characterized by a linear arrangement of three nitrogen atoms, rendering them structurally distinct from their cyclic counterparts. This study investigates the efficacy of triazenes against malaria and explores their antimicrobial activity. Preliminary results revealed significant antimalarial activity of the triazenes, as evidenced by in vitro screening against P. falciparum, the causative agent of malaria. Furthermore, the compounds exhibited broad-spectrum antimicrobial activity, indicating their potential as effective antimicrobial agents. These compounds have shown inhibitory effects on various essential enzymes and processes involved in parasite survival, replication, and transmission. The mechanism of action of triazenes against malaria involves interactions with critical molecular targets, such as enzymes involved in the parasite's metabolic pathways and proteins responsible for host cell invasion. The antimicrobial activity of the triazenes against bacteria and fungi was investigated through disc diffusion screening. The antimicrobial efficacy of triazenes has been observed against both Gram-positive and Gram-negative bacteria, as well as multidrug-resistant strains, making them potential candidates for combating drug-resistant infections. Furthermore, triazenes possess favourable physicochemical properties, such as good stability, solubility, and low toxicity, which are essential for drug development. The structural versatility of triazenes allows for the modification of their chemical composition to enhance their potency, selectivity, and pharmacokinetic properties. These modifications can be tailored to target specific pathogens, increasing the potential for personalized treatment strategies. In conclusion, this study highlights the potential of triazenes as promising candidates for the development of novel antimalarial and antimicrobial therapeutics. Further investigations are necessary to determine the structure-activity relationships and optimize the pharmacological properties of these compounds. The results warrant additional research, including MIC studies, to further explore the antimicrobial activity of the triazenes. Ultimately, these findings contribute to the development of more effective strategies for combating malaria and microbial infections.

Keywords: malaria, anti-microbials, triazene, resistance

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Authors: Chupicai Manuel

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The global efforts to end child labour have been increasingly challenged by adages of global capitalism, inequalities and poverty affecting the global south. In the face the of rising inequalities whose origin can be explained from historical and political economy analysis between the poor and the rich countries, child labour is also on the rise particularly on the global south. The socio-economic and political context of Zimbabwe has undergone serious transition from colonial times through the post-independence normally referred to as the transition period up to the present day. These transitions have aided companies and entities in the business and agriculture sector to exploit child labour while country provided conditions that enhance child labour due to vulnerability of children and anomic child welfare system that plagued the country. Children from marginalised communities dominated by plantations and farms are affected most. This paper explores the experiences and perceptions of children working in tea estates, plantations and farms, and the adults who formerly worked in these plantations during their childhood to share their experiences and perceptions on child labour in Zimbabwe. Childhood theories that view children as apprentices and a human rights perspectives were employed to interrogate the concept of childhood, child labour and poverty alleviation strategies. Phenomenological research design was adopted to describe the experiences of children working in plantations and interpret the meanings they have on their work and livelihoods. The paper drew form 30 children from two plantations through semi-structured interviews and 15 key informant interviews from civil society organisations, international labour organisation, adults who formerly worked in the plantations and the personnel of the plantations. The findings of the study revealed that children work on the farms as an alternative model for survival against economic challenges while the majority cited that poverty compel them to work and get their fees and food paid for. Civil society organisations were of the view that child rights are violated and the welfare system of the country is malfunctional. The perceptions of the majority of the children interviewed are that the system on the plantations is better and this confirmed the socio-constructivist theory that views children as apprentices. The study recommended child sensitive policies and welfare regime that protects children from exploitation together with policing and legal measures that secure child rights.

Keywords: child labour, child rights, phenomenology, poverty reduction

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Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

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Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

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Authors: Tanima Chatterjee, Maitree Bhattacharyya

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The global challenge of type 2 diabetes mellitus is a major health concern in this millennium, and researchers are continuously exploring new targets to develop a novel therapeutic strategy. Type 2 diabetes mellitus (T2DM) is often coupled with dyslipidemia increasing the risks for cardiovascular (CVD) complications. Enhanced oxidative and nitrosative stresses appear to be the major risk factors underlying insulin resistance, dyslipidemia, β-cell dysfunction, and T2DM pathogenesis. Autophagy emerges to be a promising defense mechanism against stress-mediated cell damage regulating tissue homeostasis, cellular quality control, and energy production, promoting cell survival. In this study, we have attempted to explore the pivotal role of autophagy in T2DM subjects with or without dyslipidemia in peripheral blood mononuclear cells and insulin-resistant HepG2 cells utilizing flow cytometric platform, confocal microscopy, and molecular biology techniques like western blotting, immunofluorescence, and real-time polymerase chain reaction. In the case of T2DM with dyslipidemia higher population of autophagy, positive cells were detected compared to patients with the only T2DM, which might have resulted due to higher stress. Autophagy was observed to be triggered both by oxidative and nitrosative stress revealing a novel finding of our research. LC3 puncta was observed in peripheral blood mononuclear cells and periphery of HepG2 cells in the case of the diabetic and diabetic-dyslipidemic conditions. Increased expression of ATG5, LC3B, and Beclin supports the autophagic pathway in both PBMC and insulin-resistant Hep G2 cells. Upon blocking autophagy by 3-methyl adenine (3MA), the apoptotic cell population increased significantly, as observed by caspase‐3 cleavage and reduced expression of Bcl2. Autophagy has also been evidenced to control oxidative stress-mediated up-regulation of inflammatory markers like IL-6 and TNF-α. To conclude, this study elucidates autophagy to play a protective role in the case of diabetes mellitus with dyslipidemia. In the present scenario, this study demands to have a significant impact on developing a new therapeutic strategy for diabetic dyslipidemic subjects by enhancing autophagic activity.

Keywords: autophagy, apoptosis, dyslipidemia, reactive oxygen species, reactive nitrogen species, Type 2 diabetes

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Authors: Anne-Loes K. Warps, Rob A. E. M. Tollenaar, Pieter J. Tanis, Jan Willem T. Dekker

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Anastomotic leakage after colorectal cancer surgery remains a severe complication. Early diagnosis and treatment are essential to prevent further adverse outcomes. In the literature, it has been suggested that earlier reintervention is associated with better survival, but anastomotic leakage can occur with a highly variable time interval to index surgery. This study aims to evaluate the time-interval between rectal cancer resection with primary anastomosis creation and reoperation, in relation to short-term outcomes, stratified for the use of a defunctioning stoma. Methods: Data of all primary rectal cancer patients that underwent elective resection with primary anastomosis during 2013-2019 were extracted from the Dutch ColoRectal Audit. Analyses were stratified for defunctioning stoma. Anastomotic leakage was defined as a defect of the intestinal wall or abscess at the site of the colorectal anastomosis for which a reintervention was required within 30 days. Primary outcomes were new stoma construction, mortality, ICU admission, prolonged hospital stay and readmission. The association between time to reoperation and outcome was evaluated in three ways: Per 2 days, before versus on or after postoperative day 5 and during primary versus readmission. Results: In total 10,772 rectal cancer patients underwent resection with primary anastomosis. A defunctioning stoma was made in 46.6% of patients. These patients had a lower anastomotic leakage rate (8.2% vs. 11.6%, p < 0.001) and less often underwent a reoperation (45.3% vs. 88.7%, p < 0.001). Early reoperations (< 5 days) had the highest complication and mortality rate. Thereafter the distribution of adverse outcomes was more spread over the 30-day postoperative period for patients with a defunctioning stoma. Median time-interval from primary resection to reoperation for defunctioning stoma patients was 7 days (IQR 4-14) versus 5 days (IQR 3-13 days) for no-defunctioning stoma patients. The mortality rate after primary resection and reoperation were comparable (resp. for defunctioning vs. no-defunctioning stoma 1.0% vs. 0.7%, P=0.106 and 5.0% vs. 2.3%, P=0.107). Conclusion: This study demonstrated that early reinterventions after anastomotic leakage are associated with worse outcomes (i.e. mortality). Maybe the combination of a physiological dip in the cellular immune response and release of cytokines following surgery, as well as a release of endotoxins caused by the bacteremia originating from the leakage, leads to a more profound sepsis. Another explanation might be that early leaks are not contained to the pelvis, leading to a more profound sepsis requiring early reoperations. Leakage with or without defunctioning stoma resulted in a different type of reinterventions and time-interval between surgery and reoperation.

Keywords: rectal cancer surgery, defunctioning stoma, anastomotic leakage, time-interval to reoperation

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Authors: Heather Fulford, Melanie Liddell

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The recruitment and retention of high quality employees can prove to be challenging for social enterprises, particularly in some of the core business support functions such as marketing, communications, IT and finance. This holds true for social enterprises in urban contexts, where roles with more attractive remuneration in these business functions can often be found quite readily in the private sector. For social enterprises situated in rural locations, the challenges of staff recruitment and retention are even more acute. Such challenges can lead to a skills deficit in rural social enterprises, which can, at best, hinder their growth potential, and worse, jeopardise their chances of survival. This in turn, can have a negative impact on the sustainability and resilience of the surrounding rural community in which the social enterprise is located. The purpose of this paper is to report on aspects of a collaborative initiative established to stimulate innovation and business growth in remote rural businesses in Scotland. Launched in 2010, this initiative was designed to attract young students and graduates from the region to stay in the region upon completion of their studies, and to attract others from outside the region to re-locate there post-university. To facilitate this, SMEs in the region were offered wage subsidies to encourage them to recruit a student or graduate on a work placement for up to one year to participate in an innovation or business growth-oriented project. A number of the employers offering work placements were social enterprises. Through analysis of the placement project and role specifications devised by the participating social enterprises, an overview is provided of their business development needs and the skills they require to stimulate innovation and growth. Scrutiny of the reflective accounts compiled by the students and graduates at the close of their work placements highlights the benefits they derived from being able to put their academic knowledge and skills into action within a social enterprise. Examination of interviews conducted with a sample of placement employers reveals the contribution the students and graduates made during the business development projects with the social enterprises. The challenges of hosting such placements are also discussed. The paper concludes with indications of the lessons learned and an outline of the wider implications for other remote rural locations in which social enterprises play an important role in the local economy and life of the community.

Keywords: resilience, rural development, regeneration, regional development, recruitment, resource management, retention, remuneration

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Authors: H. Pegram, R. Stevens, L. De Girolamo

Abstract:

Aligned electrospun nanofibres act as effective neuronal and glial cell scaffolds that can be layered to contain multiple sheets harboring different cell populations. This allows personalised biofunctional prostheses to be manufactured with both acellular and cellularised layers for the treatment of spinal cord injury. Additionally, the manufacturing route may be configured to produce in-vitro 3D cell based model of spinal cord injury to aid drug development and enhance prosthesis performance. The goal of this investigation was to optimise the multi-layer scaffold design parameters for prosthesis manufacture, to enable the development of multi-layer patient specific implant therapies. The work has also focused on the fabricating aligned nanofibre scaffolds that promote in-vitro neuronal and glial cell population growth, cell-to-cell interaction and long-term survival following trauma to mimic an in-vivo spinal cord lesion. The approach has established reproducible lesions and has identified markers of trauma and regeneration marked by effective neuronal migration across the lesion with glial support. The investigation has advanced the development of an in-vitro model of traumatic spinal cord injury and has identified a route to manufacture prostheses which target the repair spinal cord injury. Evidence collated to investigate the multi-layer concept suggests that physical cues provided by nanofibres provide both a natural extra-cellular matrix (ECM) like environment and controls cell proliferation and migration. Specifically, aligned nanofibre layers act as a guidance system for migrating and elongating neurons. On a larger scale, material type in multi-layer systems also has an influence in inter-layer migration as cell types favour different material types. Results have shown that layering nanofibre membranes create a multi-level scaffold system which can enhance or prohibit cell migration between layers. It is hypothesised that modifying nanofibre layer material permits control over neuronal/glial cell migration. Using this concept, layering of neuronal and glial cells has become possible, in the context of tissue engineering and also modelling in-vitro induced lesions.

Keywords: electrospinning, layering, lesion, modeling, nanofibre

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