Abstract 103: TBX20 Activates Cardiac Maturation Gene Programs Promoting Direct Human Cardiac Reprogramming

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Yang Zhou ◽  
Yawen Tang ◽  
Vladimir G Fast ◽  
Lianzhong Zhao ◽  
Rui Lu ◽  
...  

Direct cardiac reprogramming to generate induced cardiomyocyte like cells (iCMs) from fibroblasts has emerged as a promising therapeutic strategy for the treatment of heart failure, which is still the leading cause of mortality and morbidity in developed countries. While much is known regarding iCMs generated from mouse cells, the adaptation of direct cardiac reprogramming to human cells is hurdled with low efficiency and poor quality because of intrinsic differences between species. Recently, our single cell transcriptomic analysis during human direct cardiac reprogramming demonstrated the immature features of human iCMs (hiCMs) compared to endogenous cardiomyocytes (CMs) at the transcriptome level, suggesting that key factors required for CM maturation remain unidentified. We then utilized computational analyses of genomic and epigenomic data to identify the regulators underexpressed in hiCMs comparing to CMs derived from human heart tissue or stem cell differentiation. Among them, the top hit is T-box family transcription factor TBX20, whose role in direct cardiac reprogramming remains to be explored. Supplementing TBX20 in reprogramming cocktails, we found significantly increased sarcomeric protein expression, like αMHC and αActinin in hiCMs and the formation of well-organized myofibrils. TBX20’s effect has also been supported by transcriptomic analysis, where we found TBX20 activates a large number of underexpressed genes associated with sarcomere structure and ion channels, such as MYH7 , MYL2 , MYBPC3, SCN5A and KCNQ1 , suggesting that TBX20 likely enhances maturation and contractility of hiCMs. We also found that TBX20 cannot replace any of the reprogramming factors, suggesting that its potential role is complimentary to and interacting with the current cocktail. Moreover, known TBX20 targets showed inconsistent alteration in TBX20-transduced hiCMs, suggesting its novel regulation in a direct reprogramming setting. These findings assign a novel reprogramming factor TBX20 playing an essential role in generating mature hiCMs by establishing gene programs associated with cardiac muscle contractility.

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 298-302
Author(s):  
Robert H. Mak ◽  
Wai Cheung

Cachexia is common in end-stage renal disease (ESRD) patients, and it is an important risk factor for poor quality of life and increased mortality and morbidity. Chronic inflammation is an important cause of cachexia in ESRD patients. In the present review, we examine recent evidence suggesting that adipokines or adipocytokines such as leptin, adiponectin, resistin, tumor necrosis factor α, interleukin-6, and interleukin-1β may play important roles in uremic cachexia. We also review the physiology and the potential roles of gut hormones, including ghrelin, peptide YY, and cholecystokinin in ESRD. Understanding the molecular pathophysiology of these novel hormones in ESRD may lead to novel therapeutic strategies.


2021 ◽  
Vol 7 (5) ◽  
pp. 2827-2847
Author(s):  
Li Jian ◽  
Zhang Lu

With the increasingly fierce market competition, China’s tobacco industry has been severely tested. At the same time, according to the latest report of global Logistics Performance Index (LPI), there is a significant difference between China’s LPI and other developed countries, indicating that China’s logistics has low efficiency, high input and low output. How to improve the service level and operation efficiency of tobacco enterprises by strengthening the construction of logistics infrastructure network is an urgent problem for tobacco enterprises to solve. Therefore, DEA model and Malmquist index model are adopted in this paper to measure the logistics efficiency of Chinese tobacco enterprises from the aspect of logistics infrastructure network construction. This paper analyzes the state of logistics efficiency and the reasons of low efficiency in some economic regions and puts forward countermeasures and suggestions to improve the logistics efficiency of tobacco enterprises based on the construction of logistics infrastructure network.


2021 ◽  
Vol 14 (4) ◽  
pp. e240429
Author(s):  
Catarina Mendes Silva ◽  
Joana Paixão ◽  
Pedro Neves Tavares ◽  
João Pedro Baptista

Ludwig’s angina is a deep neck space infection defined as a rapidly progressive bilateral cellulitis of the submandibular space. In spite of being an uncommon entity in developed countries and the reduction of mortality and morbidity due to modern era of antibiotics, improved imaging and airway management, it is still an important and potentially life-threatening condition. The authors present 3 cases of Ludwig’s angina that occurred in a developed country, and that required admission in intensive care unit and extensive surgical and medical treatment.


Author(s):  
Neeta Baporikar

Higher education is not necessary for economic growth and development is a general presumption, the belief being literacy and primary education is. Increased concerns for ‘Education for All', also led to overall neglect of higher education in many developing countries. But given the inter-dependence of one layer of education on the other, higher education becomes critically important for developing and sustaining a good quality primary and secondary education. It is also a necessary feature for economic growth, development and sustenance. Higher education system suffers from a yawning gap in funds, outdated regulatory mechanisms, poor quality, and low efficiency. Liberalization of sector to attract large scale investments is the key to access, affordability, and equity. However, the core issue still remains ‘quality in higher education'. This chapter through in depth literature review and content analysis delves into stakeholder approach for quality higher education, which would hopefully not only optimize the higher education impact but also guarantee quality higher education.


2016 ◽  
Vol 5 (12) ◽  
pp. 106-110
Author(s):  
Umer Tahir ◽  
Qurat Ul Ain ◽  
Rai Waqas ◽  
Irfan Bashir

Viral hepatitis is one of the common transmissible causes of chronic liver responsible for increased risk of mortality and morbidity. Hepatitis C disease has worldwide high prevalence which is more fatal because of lack of vaccination availability. Present study was conducted with the aim of to address the comparative prevalence and risk factor of hepatitis C. Secondary objective was to evaluate the prevalence of this disease in Pakistan as compared to other countries. Most of the countries in the world do not have significant studies of population infected with Hepatitis C virus (HCV). During 1990-2016, 232 studies were included; containing 117 countries representing that 90% of the world population have 2.3% prevalence. According to studies, developed countries have low HCV prevalence while developing countries have high prevalence. Pakistan being a developing country has second highest HCV prevalence ranging from 4.5 to 8%. The reason of this high prevalence is unawareness about Hepatitis C in community and lack of successful therapies for patients with HCV. In past, developed countries had high prevalence but now they have low incidence because of proper system and awareness. Pakistan needs such kind of public awareness programs and better treatment facilities at affordable price to community.Tahir et al., International Current Pharmaceutical Journal, November 2016, 5(12): 106-110http://www.icpjonline.com/documents/Vol5Issue12/02.pdf


2017 ◽  
Vol 22 (3) ◽  
pp. 128-137 ◽  
Author(s):  
Norman W. Baylor

Purpose Before vaccines are marketed and used, they must be evaluated and approved by a national regulatory authority (NRA). The Food and Drug Administration (FDA) is the NRA in the USA responsible for overseeing and regulating the manufacturing, marketing, and distribution of vaccines. The paper aims to discuss this issue. Design/methodology/approach Expert review. Findings Developed countries have established governmental regulatory agencies to review and determine the safety and effectiveness of vaccines to ensure that the manufacture, sale, and use of vaccines are adequately regulated. However, even today, many developing countries do not have established NRAs. Furthermore, despite similarities, there are still substantial differences in how regulatory authorities in different countries perform minimum functions required for effective regulation of pharmaceutical products, including vaccines. The World Health Organization (WHO), although not a governmental NRA, uses a consultative approach involving its Expert Committee on Biological Standardization and Biologicals Unit to develop regulatory criteria and identify and consolidate current consensus opinions on key regulatory issues. It is through this approach that WHO informs NRAs on the necessary scientific background required to assess and advise on optimal regulatory approaches and methodologies. This paper will focus on the evolution of the US FDA and its role in regulation of vaccines to illustrate the function of a vaccine NRA. Originality/value Vaccines are an important resource for protecting people and communities from the mortality and morbidity associated with many infectious diseases. The assessment, licensure, control and surveillance of vaccines are the responsibilities of government regulatory authorities.


2009 ◽  
Vol 28 (10) ◽  
pp. 631-640 ◽  
Author(s):  
Přemysl Mladěnka ◽  
Radomír Hrdina ◽  
Zuzana Bobrovová ◽  
Vladimír Semecký ◽  
Jaroslava Vávrová ◽  
...  

Coronary heart disease and in particular its most serious form — acute myocardial infarction (AMI) — represents the most common cause of mortality in developed countries. Better prognosis may be achieved by understanding the etiopathogenetic mechanisms of AMI. Therefore, a catecholamine model of myocardial injury, which has appeared to be very similar to AMI in human in some aspect, was used. Male Wistar:Han rats were randomly divided into two groups: control group (saline) and isoprenaline group (ISO; synthetic catecholamine, 100 mg.kg— 1 subcutaneously [s.c.]). After 24 hours, functional parameters were measured, biochemical markers in the blood and metals content in the heart tissue were analysed and histological examination was performed. ISO caused marked myocardial injury that was associated with myocardial calcium overload. Close correlation between myocardial impairment (i.e. serum TnT, stroke volume index and wet ventricles weight) and the levels of myocardial calcium was observed. Direct reactive oxygen species (ROS) involvement was documented only by non-significant increase in malonyldialdehyde 24 hours after ISO injury. Moreover, myocardial element analysis revealed no significant changes as for the content of zinc and iron while selenium and copper increased in the ISO group although it reached statistical significance only for the latter.


2021 ◽  
Vol 3 (3) ◽  
pp. 994-1056
Author(s):  
Rodolfo Paolucci ◽  
André Pereira Neto

The Internet is a major source of health information, but the poor quality of the information has been criticized for decades. We looked at methods for assessing the quality of health information, updating the findings of the first systematic review from 2002. We searched 9 Health Sciences, Information Sciences, and multidisciplinary databases for studies. We identified 7,718 studies and included 299. Annual publications increased from 9 (2001) to 53 (2013), with 89% from developed countries. We identified 20 areas of knowledge. Six tools have been used worldwide, but 43% of the studies did not use any of them. The methodological framework of criteria from the first review has been the same. The authors were the evaluators in 80% of the studies. This field of evaluation is expanding. No instrument simultaneously covers the evaluation criteria. There is still a need for a methodology involving experts and users and evidence-based indicators of accuracy.


Author(s):  
Nikolay Ambrosov ◽  
Marina Markina

A study of three economic systems: a free market, a planned economy and a mixed economic system was carried out. The types of economies of the most developed countries were determined as a mixed type of economy. This type of system is more stable, since it contains the stabi­lity of a planned economy and the efficiency of a market economy. The authors base their research on the scientists’ opinion that the ratio of the economic activity of the state and the large business as a planned core of the economy and the market sector, which is represented by small and medium businesses, is a determining factor in achieving positive dynamics. Thus, it becomes necessary to identify the optimal level of this ratio. Since the organization level of developed countries can be considered formed, it is assumed that there are factors contributing to this state. Having identified these factors, we can formulate an effective development strategy for countries. It is assumed that the results of the study can help determine the development strategies of both transiti­onal economies and those that demonstrate poor quality of functioning.


2020 ◽  
Vol 7 (12) ◽  
pp. 745-749
Author(s):  
Mehmet Patmano ◽  
Durmuş Ali Çetin ◽  
Tufan Gümüş ◽  
Hasan Elkan

Objective:   Obesity, which is considered as a chronic disease today, has become an epidemic problem especially in developed countries. Laparoscopic sleeve gastrectomy (LSG) is currently one of the most common bariatric procedures in obesity treatment. This study aimse aims to present our demographic, clinical, histopathological and postoperative early and late complications of patients who underwent LSG. Material and Methods: Patients who underwent LSG due to obesity between March 2018 and December 2019 in our clinic were included in the study. The patients' age, gender, comorbid diseases, preoperative body mass index (BMI) and length of hospital stay, postoperative complications and pathology results were recorded retrospectively. Results: Of the 278 patients included in the study, 201 (72.3%) were female, 77 (27.6%) were male and the mean age was 36.2 (min: 18-max: 60 years). The mean BMI of the patients was 46.4 (min: 35.2-max: 75.1). The average hospital stay of the patients was 4.2 days (3-13 days). When the early and late complications of the patients are examined; It was observed that 25 (8.9%) patients developed early postoperative complications, and 2 (0.7%) patients developed late postoperative complications. Conclusion: LSG is a reliable surgical method with low mortality and morbidity rates. It is important that we do not have mortality and that our morbidity is within acceptable limits. Bariatric surgery is an effective and reliable application in the treatment of obesity and metabolic surgery today, in terms of its results, if the right patient is selected and performed in experienced centers.


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