Direct exposure of postimplantation mouse embryos to 5-bromodeoxyuridine in vitro and its effect on subsequent chondrogenesis in the limbs

Development ◽  
1976 ◽  
Vol 36 (3) ◽  
pp. 623-638
Author(s):  
Narsingh D. Agnish ◽  
Devendra M. Kochhar

As maternally administered 5-bromodeoxyuridine (BudR) is very quickly degraded by the liver, a combination of whole embryo culture and organ culture techniques was adopted to expose postimplantation mouse embryos to the analog and to study the effects of long-term treatment on the subsequent differentiation of limb-buds. Early and mid-11th-day mouse embryos were exposed to increasing concentrations of BudR for 12 or 24 h. Forelimbs of the treated embryos were then organ-cultured in drug-free medium and the extent of cartilage development in the explants examined. Exposure of embryos to 50–150µg/ml of BudR for 24 h resulted in significant inhibition of chondrogenesis in the subsequent limb cultures and the effect was related to dose. After treatment with 150 µg/ml of the drug, the forelimbs of the early 11-day embryos (somite stage 26–29) showed an almost complete lack of cartilage, while the limbs of mid-11th-day embryos (somite stage 32–34) were not nearly as sensitive and exhibited about 50% reduction in the amount of cartilage development. We conclude that if embryos in which the limb development is at a very early stage of development are exposed to BudR, the future course of limb differentiation is permanently and irreversibly damaged, resulting in a partial or even complete suppression of chondrogenesis in the organ. As both the dose and perhaps also the duration of treatment were critical, we suggest that the rather low frequency of reported limb malformations after in vivo injection of teratological doses of BudR may be due to only a small amount of the chemical reaching the embryos.

Reproduction ◽  
2007 ◽  
Vol 133 (2) ◽  
pp. 415-422 ◽  
Author(s):  
Satish Kumar Adiga ◽  
Megumi Toyoshima ◽  
Tsutomu Shimura ◽  
Jun Takeda ◽  
Norio Uematsu ◽  
...  

Within minutes of the induction of DNA double-strand breaks in somatic cells, histone H2AX becomes phosphorylated in the serine 139 residue at the damage site. The phosphorylated H2AX, designated as γ-H2AX, is visible as nuclear foci in the irradiated cells which are thought to serve as a platform for the assembly of proteins involved in checkpoint response and DNA repair. It is known that early stage mammalian embryos are highly sensitive to radiation but the mechanism of radiosensitivity is not well understood. Thus, we investigated the damage response of the preimplantation stage development by analyzing focus formation of γ-H2AX in mouse embryos γ-irradiated in utero. Our analysis revealed that although H2AX is present in early preimplantation embryos, its phosphorylation after 3 Gy γ-irradiation is hindered up to the two cell stage of development. When left in utero for another 24–64 h, however, these irradiated embryos showed delayed phosphorylation of H2AX. In contrast, phosphorylation of H2AX was readily induced by radiation in post-compaction stage embryos. It is possible that phosphorylation of H2AX is inefficient in early stage embryos. It is also possible that the phosphorylated H2AX exists in the dispersed chromatin structure of early stage embryonic pronuclei, so that it cannot readily be detected by conventional immunostaining method. In either case, this phenomenon is likely to correlate with the lack of cell cycle arrest, apoptosis and high radiosensitivity of these developmental stages.


Development ◽  
1990 ◽  
Vol 110 (2) ◽  
pp. 331-342 ◽  
Author(s):  
H. Ichijo ◽  
S. Fujita ◽  
T. Matsuno ◽  
H. Nakamura

Retinotectal projection is precisely organized in a retinotopic manner. In normal projection, temporal retinal axons project to the rostral part of the tectum, and nasal axons to the caudal part of the tectum. The two-dimensional relationship between the retina and the tectum offers a useful experimental system for analysis of neuronal target recognition. We carried out rotation of the tectal primordium in birds at an early stage of development, around the 10-somite stage, to achieve a better understanding of the characteristics of target recognition, especially the rostrocaudal specificity of the tectum. Our results showed that temporal retinal axons projected to the rostral part of the rotated tectum, which was originally caudal, and that nasal axons projected to the caudal part of the rotated tectum, which was originally rostral. Therefore, the tectum that had been rotated at the 10-somite stage received normal topographic projection from the retinal ganglion cells. Rostrocaudal specificity of the tectum for target recognition is not determined by the 10-somite stage and is acquired through interactions between the tectal primordium and its surrounding structures.


2019 ◽  
Vol 9 (1) ◽  
pp. 13-20
Author(s):  
Ahmed A. Aldarmahi ◽  
Mohammed W. Al-Rabia ◽  
Nada Khaled Abuarab

Background: To investigate the development of two-cell mouse embryos in vitro at different external environment factors (osmolarity) and demonstrate if the embryo at early stage of development is sensitive to osmotic stress or not. Methods: A total of 173 mouse embryos were collected during the period of January 2018 until July 2018. One NMRI male mouse was caged with the female mice CD1 for natural mating. Th e female mice were flushed of the two-cell embryos from the oviduct after 24 hours. Th e mating was confirmed by the presence of a plug in the vagina (whitish gelatine substance in the vagina) next day. Th e osmolarity values were measured by advanced micro-osmometer. One-way ANOVA test was used to compare between different values of osmolarity. Results: The findings indicated that the increased osmotic pressure can significantly affect the rate of development. The developmental rate of two-cell mouse embryos was significantly decreased when cultured in 310 milliosmole and significantly increased in 280 milliosmoles as compared to the 260 milliosmole control group (9.52 ± 16.49, P < 0.001; 83.3 ± 28.7 to 76.29 ± 31.92, P < 0.001). Conclusion: The study has concluded that the osmotic pressure can affect the rate of development and it depends on the quality of environment. Th e data observed from the mouse embryos might also be helpful in humans and shed light on the effect towards human embryos.


Author(s):  
Menghan TAO ◽  
Ning XIAO ◽  
Xingfu ZHAO ◽  
Wenbin LIU

New energy vehicles(NEV) as a new thing for sustainable development, in China, on the one hand has faced the rapid expansion of the market; the other hand, for the new NEV users, the current NEVs cannot keep up with the degree of innovation. This paper demonstrates the reasons for the existence of this systematic challenge, and puts forward the method of UX research which is different from the traditional petrol vehicles research in the early stage of development, which studies from the user's essence level, to form the innovative product programs which meet the needs of users and being real attractive.


2009 ◽  
Vol 101 (04) ◽  
pp. 674-681 ◽  
Author(s):  
Massimo Franchini ◽  
Annarita Tagliaferri ◽  
Antonio Coppola

SummaryA four-decade clinical experience and recent evidence from randomised controlled studies definitively recognised primary prophylaxis, i.e. the regular infusion of factor concentrates started after the first haemarthrosis and/or before the age of two years, as the first-choice treatment in children with severe haemophilia. The available data clearly show that preventing bleeding since an early age enables to avoid or reduce the clinical impact of muscle-skeletal impairment from haemophilic arthropathy and the related consequences in psycho-social development and quality of life of these patients. In this respect, the aim of secondary prophylaxis, defined as regular long-term treatment started after the age of two years or after two or more joint bleeds, is to avoid (or delay) the progression of arthropathy. The clinical benefits of secondary prophylaxis have been less extensively studied, especially in adolescents and adults; also in the latter better outcomes and quality of life for earlier treatment have been reported. This review summarises evidence from literature and current clinical strategies for prophylactic treatment in patients with severe haemophilia, also focusing on challenges and open issues (optimal regimen and implementation, duration of treatment, long-term adherence and outcomes, cost-benefit ratios) in this setting.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Danielle M. Nash ◽  
Zohra Bhimani ◽  
Jennifer Rayner ◽  
Merrick Zwarenstein

Abstract Background Learning health systems have been gaining traction over the past decade. The purpose of this study was to understand the spread of learning health systems in primary care, including where they have been implemented, how they are operating, and potential challenges and solutions. Methods We completed a scoping review by systematically searching OVID Medline®, Embase®, IEEE Xplore®, and reviewing specific journals from 2007 to 2020. We also completed a Google search to identify gray literature. Results We reviewed 1924 articles through our database search and 51 articles from other sources, from which we identified 21 unique learning health systems based on 62 data sources. Only one of these learning health systems was implemented exclusively in a primary care setting, where all others were integrated health systems or networks that also included other care settings. Eighteen of the 21 were in the United States. Examples of how these learning health systems were being used included real-time clinical surveillance, quality improvement initiatives, pragmatic trials at the point of care, and decision support. Many challenges and potential solutions were identified regarding data, sustainability, promoting a learning culture, prioritization processes, involvement of community, and balancing quality improvement versus research. Conclusions We identified 21 learning health systems, which all appear at an early stage of development, and only one was primary care only. We summarized and provided examples of integrated health systems and data networks that can be considered early models in the growing global movement to advance learning health systems in primary care.


Publications ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 14
Author(s):  
Eirini Delikoura ◽  
Dimitrios Kouis

Recently significant initiatives have been launched for the dissemination of Open Access as part of the Open Science movement. Nevertheless, two other major pillars of Open Science such as Open Research Data (ORD) and Open Peer Review (OPR) are still in an early stage of development among the communities of researchers and stakeholders. The present study sought to unveil the perceptions of a medical and health sciences community about these issues. Through the investigation of researchers` attitudes, valuable conclusions can be drawn, especially in the field of medicine and health sciences, where an explosive growth of scientific publishing exists. A quantitative survey was conducted based on a structured questionnaire, with 179 valid responses. The participants in the survey agreed with the Open Peer Review principles. However, they ignored basic terms like FAIR (Findable, Accessible, Interoperable, and Reusable) and appeared incentivized to permit the exploitation of their data. Regarding Open Peer Review (OPR), participants expressed their agreement, implying their support for a trustworthy evaluation system. Conclusively, researchers need to receive proper training for both Open Research Data principles and Open Peer Review processes which combined with a reformed evaluation system will enable them to take full advantage of the opportunities that arise from the new scholarly publishing and communication landscape.


Author(s):  
Chuan De Foo ◽  
Shilpa Surendran ◽  
Geronimo Jimenez ◽  
John Pastor Ansah ◽  
David Bruce Matchar ◽  
...  

The primary care network (PCN) was implemented as a healthcare delivery model which organises private general practitioners (GPs) into groups and furnished with a certain level of resources for chronic disease management. A secondary qualitative analysis was conducted with data from an earlier study exploring facilitators and barriers GPs enrolled in PCN’s face in chronic disease management. The objective of this study is to map features of PCN to Starfield’s “4Cs” framework. The “4Cs” of primary care—comprehensiveness, first contact access, coordination and continuity—offer high-quality design options for chronic disease management. Interview transcripts of GPs (n = 30) from the original study were purposefully selected. Provision of ancillary services, manpower, a chronic disease registry and extended operating hours of GP practices demonstrated PCN’s empowering features that fulfil the “4Cs”. On the contrary, operational challenges such as the lack of an integrated electronic medical record and disproportionate GP payment structures limit PCNs from maximising the “4Cs”. However, the enabling features mentioned above outweighs the shortfalls in all important aspects of delivering optimal chronic disease care. Therefore, even though PCN is in its early stage of development, it has shown to be well poised to steer GPs towards enhanced chronic disease management.


2021 ◽  
pp. 026666692199750
Author(s):  
Noore Alam Siddiquee ◽  
Md Gofran Faroqi

This paper explores the impacts of Bangladesh’s Union Digital Centers (UDCs) as government information and service delivery hubs in rural areas. Drawing on user-surveys and semi-structured individual interviews it demonstrates that the UDCs have produced generally positive yet modest impacts on governance of service delivery. It shows that the UDCs are at an early stage of development, and that they offer only a limited set of services. While they helped extend ICT-enabled services to sections of population that would otherwise have missed them, the UDCs do not have much to do with rural livelihoods and empowerment of the poor and marginalized groups. These findings point to current inadequacies and pitfalls of the UDC approach to development. We argue that enhanced viability and effectiveness of the UDC experiment would warrant embedding more value-added governmental services and further strengthening of their capacity, mandate, and connectivity with government agencies at various levels, among others.


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