Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Reviews
Year : 2008 | Month : June | Volume : 2 | Issue : 3 | Page : 871 - 878 Full Version

Strategies And Vectors For Gene Therapy: Its Prospective Therapeutic Attributes Against Restenosis


Published: June 1, 2008 | DOI: https://doi.org/10.7860/JCDR/2008/.261
KHANNA A*
Correspondence Address :
Dr. Khanna A ,Medical Genetics, MD/PhD Research Fellow , IMT University of Tampere, Tampere,Finland. E-mail: anchit.khanna@gmail.com

Abstract

Gene therapy is seen as one of the upcoming technologies not only against diseases which have monogenetic etiology, but also against complex diseases such as cancer and cardiovascular disorders. Amongst the cardiovascular disorders, restenosis is one of many disorders which has seen a major increase in the clinical trials, using gene therapy, in recent years. Restenosis, which is simply reoccurrence of stenosis, is seen mainly post surgically in an artery or blood vessel which had been unblocked. Importantly, even though stents have been introduced to prevent restenosis to occur post surgically, the effect seems to be limited to decreasing the statistical rate , and restenosis still persists as a problem for which a definite solution or remedy, acting on the very roots of its pathogenesis, is the need of the hour. Gene therapy, transfer of a healthy gene for curing a disorder, seems to a promising modality for the purpose. To meet this end a definite strategy, an appropriate vector and target for efficient and persistent expression of the healthy gene in the desired or localized area, is what will make gene therapy against restenosis more effective.

Keywords

Restenosis, Gene therapy, Vector, Remodeling

Introduction
About 40-50% of vessels undergo Restenosis after Coronary Artery Bypass Graft (CABG) or Percutaneous Coronary Angioplasty (PTCA), and in occasions where traditional stents are used (.i.e. when the diameter of the vessel is > 3mm in diameter) this rate is reduced to 20% -30% (1). This loss of lumen in a previously operated / dilated artery which results in poor vascular patency is due to increase in number of intimal (inner layer of the vessel) cells, known as neointimal hyperplasia. Neointimal hyperplasia along with constrictive remodeling are the two phenomenons responsible for restenosis, and in both, extra cellular matrix (ECM) accumulation is the causative factor (90% of the bulk of neointima comprises of ECM). Constrictive remodeling is said to be the major cause for this luminal loss, especially vessels which have been dilated due to atherosclerosis as the primary cause (1). This remodeling can be prevented by transferring a healthy gene, into the patient’s body, which is thought to be playing a pivotal role in its formation. One of the key challenges at present is finding the appropriate vector for delivering a healthy gene or a cocktail of genes (multigenic approach) in the target tissue. Another aspect that needs to be considered is the duration of the gene expression, post gene delivery, by the vector.

Material and Methods

Strategies For Gene Delivery
Cardiovascular diseases can either be inherited or acquired, and each type needs to be dealt with a different strategy (2) (Table/Fig 1) .There are basically two strategies used for the gene delivery, namely in-vivo and ex-vivo gene delivery. When therapeutic or desired genes are delivered inside the body then it is known as in-vivo gene delivery, if the cells are removed from the body and the therapeutic genes then transferred into the cells, it is termed as ex-vivo gene delivery. To achieve delivery of the desired gene or product in the target tissue certain steps need to be considered. Firstly, DNA (desired genes) must be delivered to the nucleus and secondly, the central dogma (DNARNA Protein (functional)) should follow. The first step can occur either in in-vivo or ex-vivo, but the second step always occurs within the body (in-vivo).

Ex-Vivo Gene Delivery
Ex-vivo gene delivery is a relatively simple method mainly used in vein graft failure. A good demonstration of its use was shown against familial hypercholesterolemia. The Kupffer cells (cells were taken out by partial hepatectomy) were cultured ex-vivo and then transduced with retrovirus containing the gene for LDL receptor, as a result there was decrease in cholesterol levels (3)(4). There are certain advantages with the ex-vivo gene delivery, for example, it has a high efficiency for gene transfer into the targeted cells, its specificity can be restricted to the desired cell type by careful optimization and designing and also the immune response to the vector transferring the gene is minimized as it is performed outside the host. The disadvantages for ex-vivo gene delivery may be due to the procedure involved, for example, the patient may have to undergo two invasive procedures one for the cell harvest and the other for the cell reintroduction after the transfer (like in the case of hepatocytes. (Table/Fig 2)

In-Vivo Gene Delivery
In In-vivo gene delivery there is only one procedure required, i.e., injection of the gene vector and there is no need of cell harvesting and reimplantation. Also any cell of the body organ is the potential target for the gene transfer. But there are some drawbacks with this method as well like, it will be difficult to reach to remote tissues like that of the myocardium or a narrow artery in which the vector may be washed away or the pathogenic mechanisms (e.g. ischemia) may occur before the transfer takes place. Also the systemic release of the vector would really be unavoidable and so optimization of the gene expression (localization) will also be hard to control. Also the vector may produce an immune response and result in a rejection to it, especially if the immune system has had a prior exposure to it. Keeping in mind the fact about the diversity of the cells as targets in our body, the vector system needs to be developed for individual applications (5) , and has a long way still to go to be able to give an efficient gene transfer at the same time meeting all the safety concerns.

Vectors For Gene Therapy
Vectors can be either non-viral or viral. At the moment, out of the two, non viral vectors are suggested to meet the properties of an ideal vector, simply because of it being nonpathogenic, more efficient in gene delivery and less immunogenic. Additionally, because the mechanisms, by which viral vectors work and can be controlled, requires a lot more research and better comprehension for them to be used therapeutically. But limitation of sustained gene expression by non-viral vectors needs to be addressed for it to make it to the clinical practice.

Non-Viral Vectors
This group of vectors consists of naked<

Discussion

The therapeutic attribute of gene therapy against various disorders, will require a well planned and systematic approach to be most effective. Many factors like etiology, choice of vector, mode of delivery of vector, choice of targets etc. all have to be carefully planned based on the merits of each case. Gene fingerprinting and pharmacogenomics may further accentuate its effectiveness.

At present optimization of various available vectors and search for new potential vectors is the area of focus in the field of gene therapy. More and more clinical trials are being initiated in this sector and many new strategies being tested. Many safety concerns and ethical issues have arisen with this methodology of treatment, and adverse effects like neoplasms, edema, immune responses, etc. have acted as a rate limiting step in the advancement of research in this field. But at the same time researches addressing these concerns have been very promising. Recent example being the discovery of a novel mechanism involving protein Hexon and a blood clotting enzyme ,Factor X by Dr. Baker’s group (Waddington et al) at the University of Glasgow. Mutations in the Hexon protein and pharmacological blockade of the interactions of these proteins blocked the gene transfer, suggesting the mechanism by which gene transfer takes place in case of fibre modified viral vectors (19).
This new fact can be used to design safer fiber modified vectors for gene delivery. Gene therapy could be the answer to many diseases, especially against Restenosis, for prevention of which today the most common tool are the stents. The incidence of Restenosis when no stent is used in 25-40% , but when a medicated stent is used this incidence can be brought down to 10-20%, which still is quite a considerable rate considering the number of CABGs carried out (20).

Gene therapy is one promising modality which can be combined with present modalities like coated stents ( which may no longer pose any threat of late and sudden occurrence of restenosis associated with it ) to fill this vacuum and act at the root level against restenosis .

References

1.
Fogorus RN. Restenosis after Angioplasy and stenting : About.com. Aug 2004 http://heartdisease.about.com/cs/angioplastystents/a/restenosis.htm
2.
Kaplan NM, Palmer BF, Bekeredjian R, Shohet RV. Cardiovascular gene therapy: Angiogenesis and beyond. Am J Med Sci. 2004; 139-148.
3.
Melo LG, Pachori AS, Massimiliano G, Dzau VJ. Genetic Therapies for cardiovascular diseases. Trends in Mol Med .2005; vol 11; No.5.
4.
Grossman M, Rader DJ, Muller D, et al. A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolemia. Nat Med. 1995; 1(11): 1148-1154
5.
Harvey B, Hackett N, El-Sawy T, et al. Variability of human systemic humoral immune responses to adenovirus gene transfer vectors administered to different organs. J Virol. 1993; 73: 6729–6742
6.
Aoki M et al. Angiogenesis induced by hepatocyte growth factor in non-infarcted myocardium and infarcted myocardium: up-regulation of essential transcription factors for angiogenesis. Gene Therapy 2000; 7:417-427
7.
Norman J et al. Liposome-mediated, nonviral gene transfer induces a systemic inflammatory which can exacerbate pre-existing inflammation. Gene Therapy. 2000; 7:1425-1430
8.
Thomas CE, Ehrhardt A, Kay MA. Progress and Problems with the use of viral vectors for gene therapy. Nature Genetics Vol 4: 2003; 346-357.
9.
Lawrie et al. Microbubble-enhanced ultrasound for vascular gene delivery. Gene Therapy 2000; 7:2023-2027
10.
Nabel EG. Gene Therapy for cardiovascular disease. Circulation . 1995; 91: 541-548.
11.
Maione D et al. An improved helper-dependent adenoviral vector allows persistent gene expression after intramuscular delivery and overcomes preexisting immunity to adenovirus. Proc Natl Acad Sci USA. 2001; 98: 5986-5991.
12.
Parissis JT, Nikolaou VN. Gene therapy in the Management of Cardiovascular Disease. Hellenic journal of Cardiology .2003; 44:271-276.
13.
Pislaru S, Ja

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