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Topography of a place has a significant impact on soil characteristics that ultimately influence soil iodine levels. Lower Himalayan region (LHR) in Pakistan has a wide range of climatic and geological variations. Hence, an investigation was conducted to analyze the iodine concentration and other physicochemical properties of soils in two LHR districts, Haripur and Mansehra. Spatial analysis indicated a decrease in iodine levels in the mountainous regions in comparison to the flat portions of LHR. Soil samples obtained from different locations across Haripur had a stronger affinity for iodine due to variations in solubility and adsorption of iodine to soil clay components, which can be attributed to lower pH, higher organic matter, and a higher cation exchange capacity (CEC). In contrast to the plains of Haripur, elevated locations in the Mansehra district had decreased levels of iodine, along with a higher soil pH and reduced soil organic matter. The soil erosion and depletion of soil micronutrients in the hilly region of Mansehra may be attributed to the unfavorable soil conditions and excessive precipitation. Presence of clay, iron (Fe), and aluminum (Al) in the soil led to a rise in iodine levels. Iodine concentrations exhibited an inverse relationship with soil acidity. Study revealed a direct correlation between soil iodine levels and their cation exchange capacity (CEC) and clay content. This study aims to gather fundamental data for the chosen regions of LHR to address illnesses caused by iodine deficiency.
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Yodo , Suelo , Suelo/química , Yodo/análisis , Yodo/química , Pakistán , Concentración de Iones de HidrógenoRESUMEN
Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance of immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include the appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potentially novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report.
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Trasplante de Corazón , Trasplante de Pulmón , Trasplante Heterólogo , Trasplante Heterólogo/ética , Humanos , Trasplante de Pulmón/ética , Animales , Estados Unidos , Trasplante de Corazón/ética , National Heart, Lung, and Blood Institute (U.S.) , Investigación Biomédica/ética , Donantes de Tejidos/provisión & distribución , Donantes de Tejidos/éticaRESUMEN
The collective efforts of scientists over multiple decades have led to advancements in molecular and cellular biology-based technologies including genetic engineering and animal cloning that are now being harnessed to enhance the suitability of pig organs for xenotransplantation into humans. Using organs sourced from pigs with multiple gene deletions and human transgene insertions, investigators have overcome formidable immunological and physiological barriers in pig-to-nonhuman primate (NHP) xenotransplantation and achieved prolonged pig xenograft survival. These studies informed the design of Revivicor's (Revivicor Inc, Blacksburg, VA) genetically engineered pigs with 10 genetic modifications (10 GE) (including the inactivation of 4 endogenous porcine genes and insertion of 6 human transgenes), whose hearts and kidneys have now been studied in preclinical human xenotransplantation models with brain-dead recipients. Additionally, the first two clinical cases of pig-to-human heart xenotransplantation were recently performed with hearts from this 10 GE pig at the University of Maryland. Although this review focuses on xenotransplantation of hearts and kidneys, multiple organs, tissues, and cell types from genetically engineered pigs will provide much-needed therapeutic interventions in the future.
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Animales Modificados Genéticamente , Trasplante Heterólogo , Animales , Trasplante Heterólogo/métodos , Humanos , Porcinos , Ingeniería Genética/métodos , Trasplante de Corazón/métodosRESUMEN
Purpose: Effective Altruism (EA) has become one of the most prominent socio-philosophical movements of recent years. EA is also facing intense scrutiny due to the business practices of some of its most prominent adherents. On the other hand, the dark triad traits of Machiavellianism, narcissism and psychopathy have been getting increasing attention in entrepreneurship research. There is growing evidence that these traits can motivate entrepreneurial intention. We therefore sought to investigate if there was a connection between the entrepreneurship discourse in EA and traits corresponding to dark triad behavior. Design/methodology/approach: Using a discursive analytic method, we investigated the discursive threads on entrepreneurship in EA over a 10-year period. Findings: While we believe EA brings a much-needed perspective to the overall debate on doing good, we found ample evidence that it might have promoted the sort of dark triad behavior which some evidence suggests can lead to financial success, but can equally lead to the type of morally bankrupt, unethical and even illegal practices of some entrepreneurs. We also discovered a somewhat temporal dimension in EA's discourse on entrepreneurship, beginning with discourse encouraging some risk taking and entrepreneurship, before moving on to discourses on the benefits of having a smart and illicit character, and ending with a focus on aggressive risk taking. Originality: The findings contribute to the still nascent debate on dark personality traits in entrepreneurship, and enriches the theoretical advancement of the field. However, our research differs from prior studies which were almost exclusively focused on the firm. Instead, we examine this phenomenon within a highly influential belief system/philosophical movement.
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PURPOSE OF REVIEW: The first successful pig to human cardiac xenotransplantation in January 2022 represented a major step forward in the fields of heart failure, immunology, and applied genetic engineering, using a 10-gene edited (GE) pig. This review summarizes the evolution of preclinical modelling data which informed the use of each of the 10 genes modified in the 10-GE pig: GGTA1, Β4GalNT2, CMAH, CD46, CD55, TBM, EPCR, CD47, HO-1, and growth hormone receptor. RECENT FINDINGS: The translation of the 10-GE pig from preclinical modelling to clinical compassionate xenotransplant use was the culmination of decades of research combating rejection, coagulopathy, inflammation, and excessive xenograft growth. Understanding these 10 genes with a view to their combinatorial effects will be useful in anticipated xenotransplant clinical trials.
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Trastornos de la Coagulación Sanguínea , Rechazo de Injerto , Animales , Humanos , Porcinos , Trasplante Heterólogo , Animales Modificados Genéticamente , Rechazo de Injerto/genética , Rechazo de Injerto/prevención & control , Ingeniería Genética , InflamaciónAsunto(s)
Trasplante de Órganos , Obtención de Tejidos y Órganos , Animales , Porcinos , Humanos , Primates , Donantes de Tejidos , Trasplante HeterólogoRESUMEN
Insect pests pose a major threat to agricultural production, resulting in significant economic losses for countries. A high infestation of insects in any given area can severely reduce crop yield and quality. This review examines the existing resources for managing insect pests and highlights alternative eco-friendly techniques to enhance insect pest resistance in legumes. Recently, the application of plant secondary metabolites has gained popularity in controlling insect attacks. Plant secondary metabolites encompass a wide range of compounds such as alkaloids, flavonoids, and terpenoids, which are often synthesized through intricate biosynthetic pathways. Classical methods of metabolic engineering involve manipulating key enzymes and regulatory genes to enhance or redirect the production of secondary metabolites in plants. Additionally, the role of genetic approaches, such as quantitative trait loci mapping, genome-wide association (GWAS) mapping, and metabolome-based GWAS in insect pest management is discussed, also, the role of precision breeding, such as genome editing technologies and RNA interference for identifying pest resistance and manipulating the genome to develop insect-resistant cultivars are explored, highlighting the positive contribution of plant secondary metabolites engineering-based resistance against insect pests. It is suggested that by understanding the genes responsible for beneficial metabolite compositions, future research might hold immense potential to shed more light on the molecular regulation of secondary metabolite biosynthesis, leading to advancements in insect-resistant traits in crop plants. In the future, the utilization of metabolic engineering and biotechnological methods may serve as an alternative means of producing biologically active, economically valuable, and medically significant compounds found in plant secondary metabolites, thereby addressing the challenge of limited availability.
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Fabaceae , Animales , Fabaceae/genética , Estudio de Asociación del Genoma Completo , Fitomejoramiento , Agricultura , Insectos/genéticaRESUMEN
BACKGROUND: A genetically engineered pig cardiac xenotransplantation was done on Jan 7, 2022, in a non-ambulatory male patient, aged 57 years, with end-stage heart failure, and on veno-arterial extracorporeal membrane oxygenation support, who was ineligible for an allograft. This report details our current understanding of factors important to the xenotransplantation outcome. METHODS: Physiological and biochemical parameters critical for the care of all heart transplant recipients were collected in extensive clinical monitoring in an intensive care unit. To ascertain the cause of xenograft dysfunction, we did extensive immunological and histopathological studies, including electron microscopy and quantification of porcine cytomegalovirus or porcine roseolovirus (PCMV/PRV) in the xenograft, recipient cells, and tissue by DNA PCR and RNA transcription. We performed intravenous immunoglobulin (IVIG) binding to donor cells and single-cell RNA sequencing of peripheral blood mononuclear cells. FINDINGS: After successful xenotransplantation, the graft functioned well on echocardiography and sustained cardiovascular and other organ systems functions until postoperative day 47 when diastolic heart failure occurred. At postoperative day 50, the endomyocardial biopsy revealed damaged capillaries with interstitial oedema, red cell extravasation, rare thrombotic microangiopathy, and complement deposition. Increased anti-pig xenoantibodies, mainly IgG, were detected after IVIG administration for hypogammaglobulinaemia and during the first plasma exchange. Endomyocardial biopsy on postoperative day 56 showed fibrotic changes consistent with progressive myocardial stiffness. Microbial cell-free DNA testing indicated increasing titres of PCMV/PRV cell-free DNA. Post-mortem single-cell RNA sequencing showed overlapping causes. INTERPRETATION: Hyperacute rejection was avoided. We identified potential mediators of the observed endothelial injury. First, widespread endothelial injury indicates antibody-mediated rejection. Second, IVIG bound strongly to donor endothelium, possibly causing immune activation. Finally, reactivation and replication of latent PCMV/PRV in the xenograft possibly initiated a damaging inflammatory response. The findings point to specific measures to improve xenotransplant outcomes in the future. FUNDING: The University of Maryland School of Medicine, and the University of Maryland Medical Center.
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Ensayos de Uso Compasivo , Leucocitos Mononucleares , Humanos , Masculino , Trasplante Heterólogo , Inmunoglobulinas Intravenosas , Corazón , Rechazo de Injerto/prevención & controlRESUMEN
Economic integration of ever-increasing number of immigrants in the host country is a challenge both for the immigrant and their host government. Immigrant entrepreneurship can be one of the solutions to this challenge. However, little is known about how immigrant entrepreneurship intention formation process takes place. Immigrants face various challenging situations that make them psychologically and cognitively distinct. This study models from a holistic perspective, the dimensions of individual and contextual variables as antecedents of Immigrants' entrepreneurial intention (IEI). The study aims to identify the key factors responsible for developing EI of immigrants with an implementation intent. Cross-sectional data from Canada is examined using a sample of 250 immigrants. The analysis adopts a structural equation modelling approach. In addition to risk perception, bridging social network, and experience, we postulate that the perceived distance of entrepreneurial culture (country of origin versus host country) and entrepreneurial support are crucial factors that influence IEI. Empirical analyses based on survey data partially confirmed our hypotheses. The results show the role of psychological and cognitive factors in determining immigrants' intention to start a new business. We extend the Theory of Planned Behaviour (TPB) by identifying certain understudied determinants in the literature and presenting a holistic decision-making process in the context of immigration-entrepreneurship nexus. Examining specific factors that appropriately contextualize immigrant entrepreneurship research and relativize the EI through a learning-based approach advances current literature. It offers insights to policymakers and practitioners to contemplate entrepreneurial culture as a shared liability issue (foreignness, host country), and adapt their entrepreneurship guidance accordingly. Thus, this study opens the way to a better understanding of the business behaviour of immigrants. Their impact matters for the entrepreneurial diversity that resilient ecosystems need.
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Partial heart transplantation is a new type of transplant that delivers growing heart valve replacements for babies. Partial heart transplantation differs from orthotopic heart transplantation because only the part of the heart containing the heart valve is transplanted. It also differs from homograft valve replacement because viability of the graft is preserved by tissue matching, minimizing donor ischemia times, and recipient immunosuppression. This preserves partial heart transplant viability and allows the grafts to fulfill biological functions such as growth and self-repair. These advantages over conventional heart valve prostheses are balanced by similar disadvantages as other organ transplants, most importantly limitations in donor graft availability. Prodigious progress in xenotransplantation promises to solve this problem by providing an unlimited source of donor grafts. In order to study partial heart xenotransplantation, a suitable large animal model is important. Here we describe our research protocol for partial heart xenotransplantation in nonhuman primates.
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Trasplante de Corazón , Trasplante de Órganos , Trasplantes , Animales , Trasplante Heterólogo/métodos , Primates , Trasplante de Órganos/métodos , Rechazo de InjertoRESUMEN
The building sector is one of the major contributors to greenhouse gas (GHG) emissions, which may impede the achievement of Malaysia's intended nationally determined contribution (INDC) by 2030. Therefore, this paper is aimed at identifying the underlying factors that affect working adults' willingness to pay (WTP) premium prices for green buildings. Data were collected from a total of 1198 respondents and analyzed using structural equitation modeling partial least square (SEM-PLS) to measure the willingness to pay for green buildings among working adults in Malaysia. The findings reveal that environmental literacy affects environmental belief as well as awareness of consequences among working adults in Malaysia. The findings also reveal that incentives for green building buyers have a significant impact on perceived behavioral control, while awareness of consequences has a significant influence on ascription of responsibility. However, the results reveal that awareness of consequences does not influence buyers' willingness to pay for green buildings. Moreover, the ascription of responsibility and perceived behavioral control have a significant effect on willingness to pay for green buildings. The findings of this study will help the concerned authorities to take appropriate steps to promote willingness to pay for green buildings, which will contribute significantly to the realization of INDC by 2030 as part of the Paris Agreement.
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Gases de Efecto Invernadero , Factores Socioeconómicos , Paris , Malasia , Encuestas y CuestionariosAsunto(s)
Ecocardiografía , Corazón , Humanos , Animales , Porcinos , Valor Predictivo de las Pruebas , Ecocardiografía/métodosRESUMEN
Cardiac xenotransplantation from swine has been proposed to "bridge the gap" in supply for heart failure patients requiring transplantation. Recent preclinical success using genetically modified pig donors in baboon recipients has demonstrated survival greater than 6 mo, with a modern understanding of xenotransplantation immunobiology and continued experience with large animal models of cardiac xenotransplantation. As a direct result of this expertise, the Food and Drug Administration approved the first in-human transplantation of a genetically engineered cardiac xenograft through an expanded access application for a single patient. This clinical case demonstrated the feasibility of xenotransplantation. Although this human study demonstrated proof-of-principle application of cardiac xenotransplantation, further regulatory oversight by the Food and Drug Administration may be required with preclinical trials in large animal models of xenotransplantation with long-term survival before approval of a more formalized clinical trial. Here we detail our surgical approach to pig-to-primate large animal models of orthotopic cardiac xenotransplantation, and the postoperative care of the primate recipient, both in the immediate postoperative period and in the months thereafter. We also detail xenograft surveillance methods and common issues that arise in the postoperative period specific to this model and ways to overcome them. These studies require multidisciplinary teams and expertise in orthotopic transplantation (cardiac surgery, anesthesia, and cardiopulmonary bypass), immunology, genetic engineering, and experience in handling large animal donors and recipients, which are described here. This article serves to reduce the barriers to entry into a field with ever-growing enthusiasm, but demands expertise knowledge and experience to be successful.