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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
Original article / research
Full Version
Serum miRNA-30a-5p in Steroid Sensitive Idiopathic Nephrotic Syndrome in Indian Children: A Case-control Study
Correspondence Address :
Dr. Gundyadka Moideen Safwan,
Assistant Professor, Department of Paediatrics, KS Hegde Medical Academy, Deralakatte, Dakshina Kannada, Mangalore-575018, Karnataka, India.
E-mail: gmsafwan@nitte.edu.in
Introduction: Childhood Nephrotic Syndrome (NS) is a podocytopathy. Micro Ribonucleic Acid (miRNA), composed of 21-25 non coding nucleotides, regulates gene expression by inhibiting protein transcription by binding to complementary messenger RNA. The microRNA-30a is expressed in the human glomerular podocytes and collecting ducts. This microRNA protects the podocytes by targeting the Calcineurin-nuclear Factor of Activated T cells (NFATc) pathways. Serum microRNA-30a-5p is a validated biomarker which is upregulated in NS.
Aim: To determine the serum miRNA-30a-5p in steroid sensitive idiopathic NS in Indian children.
Materials and Methods: This case-control study was conducted at the Department of Paediatrics, KS Hegde Medical Academy, Mangalore, Karnataka, India, from from January 2018 to June 2019. Thirty children with NS and age and gender matched controls were recruited. Relative expression of microRNA-30a-5p was analysed by Real-Time quantitative Polymerase Chain Reaction (RT-qPCR). Estimations were done both in cases and controls at enrollment and also at four weeks when in remission in cases. The fold change was calculated as a power of cycle threshold. Statistical tests Kolmogorov-Smirnov test was used to establish the normality using Statistical Package for Social Sciences (SPSS) version 22.0.
Results: There was upregulation of microRNA-30a-5p expression among children with NS with a significant fold change (~184) at enrollment. The levels declined, but remained above baseline (~6) after four weeks of treatment when compared to controls. The mean differences in delta threshold cycle and threshold cycle between the three groups were significant (p<0.001). There was no correlation with the biochemical parameters.
Conclusion: The present study concludes that serum microRNA-30a-5p expression is upregulated in children with steroid sensitive NS in Indian children.
Delta threshold cycle, Micro ribonucleic acid, Podocytopathy, Prednisolone therapy
Childhood NS is a common glomerular disease characterised by massive selective proteinuria. Grouped under podocytopathy, immune dysregulation and systemic circulating factors are a few proposed mechanisms for the podocyte injury seen in primary idiopathic NS (1),(2). The disorder is further classified as minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy by histopathology, and steroid-sensitive and steroid-resistant by treatment response to prednisolone. Relapses occur in two-thirds of children (2).
Studies explore novel non invasive biomarkers to detect and monitor disease activity in renal diseases in children (3),(4),(5). Nearly one-third of the genome is estimated to be regulated by around 2000 miRNAs so far identified (6). The miRNAs, composed of 21-25 non coding nucleotides bind to complementary messenger RNAs and inhibit protein transcription (7). Thus, they are important in gene expression. The miRNA-30a is expressed in the human glomerular podocytes and collecting ducts (8). In mouse models, this miRNA maintains the normal podocyte morphology by targeting the calcineurin-nuclear factor of activated T cells (NFATc) pathways (8),(9),(10). The dysregulation of miRNAs results in renal injury. In children with NS, the most scrutinised miRNA is serum miRNA-30a-5p and is a validated biomarker that is upregulated in NS (11),(12),(13).
There are no Indian studies on miRNA expression in NS, and hence this study on miRNA-30a-5p expression in children with steroid sensitive NS. The children were evaluated for microRNA-30a-5p on enrollment and four weeks into prednisolone therapy in remission using RT-qPCR. The authors hypothesised an elevation in serum miRNA-30a-5p by several folds during disease state with a return to baseline after four weeks of prednisolone therapy.
A case-control study was conducted at the Department of Paediatrics, KS Hegde Medical Academy, Mangalore, Karanataka, India, from January 2018 to June 2019. Institutional Ethical Committee clearance (INST.EC/EC/075/2017-18) and written informed parental consent from all enrolled were obtained.
Sample size calculation: Sample size was determined using www.openepi.com/SampleSize/SSCC.htm assuming 95% Confidence Interval (CI) and 80% power.
Inclusion criteria: Thirty children aged between one and 18 years diagnosed as idiopathic NS were enrolled as cases either at the first episode or relapse. An equal number of healthy children, age and gender-matched were the controls.
Exclusion criteria: Congenital, infantile, secondary, and steroid resistant NS were excluded. Children with NS presenting with infections, idiopathic NS on immunosuppressant therapy other than prednisolone were also excluded.
Study Procedure
Demographic data included age, gender, clinical and lab status of NS, atypical features, and response to prednisolone therapy. Standard case definitions were used (2). The first episode of NS was diagnosed in the presence of hypoalbuminaemia (≤2.5 g/dL), oedema, hyperlipidaemia (cholesterol >200 mg/dL) with spot urine protein and creatinine ratio >2, and early morning urine protein ≥3+ on the dipstick. Relapse was defined as urine albumin ≥3+ in three consecutive early morning specimens, having been in remission previously. Remission was defined as urine albumin nil or trace in three consecutive early morning specimens. Frequent relapsers were those with ≥2 relapses in initial six months or ≥4 in a year (14).
The authors estimated the relative miRNA-30a-5p expression by RT-qPCR using glyceraldehyde 3-phosphate dehydrogenase as the reference gene. Five millilitres of blood was obtained from the cases (pretreatment group) and controls at enrollment. A second sample was obtained after four weeks only from the cases (treatment group) when in remission. The serum was separated by centrifuging at 20,000 g for 10 minutes and stored at -80°C until further processing. RNA isolation, complementary de-oxy RNA synthesis, and amplification of miRNA-30a-5p were carried out sequentially using commercial kits according to the instructions given with the kit (mirVana™ PARIS™ RNA and native protein purification kit, TaqMan® advanced miRNA cDNA synthesis kit, and TaqMan® Advanced miRNA Assays from Applied Biosystems, Thermo Fisher Scientific).
The miRNA-30a-5p expression was normalised to the reference gene by calculating the delta threshold cycle (?Ct) and further relative to the healthy controls by delta delta threshold cycle (??Ct) (15). The fold change was calculated by 2-??Ct and corrected for a ratio (16). In the present study, miRNA was considered upregulated, if there was atleast a 1.5-fold increase in NS than the control, and Ct was <35 in the control sample (11).
Statistical Analysis
Data were analysed using IBM SPSS, USA. The Kolmogorov-Smirnov test was used to establish the normality of the ?Ct data. In children with NS, miRNA-30a-5p expression was compared using the paired t-test. The comparison between the cases and the controls was made by an Independent sample t-test. A p<0.05 was considered to be significant.
A total of 60 children were recruited in the study, 30 cases of children with NS and 30 controls. The study group’s median age was seven years, with 1.03:1 male and female distribution. Sixteen (53.3%) children were included during a relapse of which seven were frequent relapsers. Atypical features like haematuria and hypertension were seen in 3.3% and 6.7% of cases, respectively (Table/Fig 1). The biochemical characteristics of the children with NS are mentioned in (Table/Fig 2). The miRNA-30a-5p expression is given in (Table/Fig 3). The results showed upregulation of the miRNA-30a-5p at enrollment. The levels declined but remained above baseline after four weeks of treatment in children with NS (Table/Fig 3). The magnitude of fold change was ~184 at enrollment, and ~6 four weeks into treatment in comparison to control. The mean differences in delta threshold cycle and threshold cycle between the three groups were significant (Table/Fig 4). There was no correlation between miRNA expression with urine protein creatinine ratio, serum albumin, or serum cholesterol. Comparison of miRNA expression within the case group, namely, between the first episode and relapse and frequent and infrequent relapses, did not show statistical significance.
The present study examined the relative expression of previously validated serum miRNA-30a-5p in idiopathic NS pretreatment and after four weeks using RT-qPCR assay in an Indian population. The results showed upregulation among cases. The enrollment cases had a significant fold change (~184) as calculated by the comparative Ct method. Despite a marked decline, the values four weeks into treatment were significantly higher (~6) compared to controls. The miRNA-30a-5p is shown to be abundant in human glomerular podocytes (8) and is protective against injury to them (17).
According to study by Luo Y et al., the concentrations of serum and urinary miR-30a-5p, were significantly increased in NS children compared with controls and the concentrations markedly declined with the clinical improvement (11). Similar observations were made by Zhang W et al., and Teng J et al. Thus, it is a validated biomarker in NS in Chinese ethnicity (11),(12),(13). Wu J et al., demonstrated the downregulation of miRNA-30a-5p by in-situ hybridisation in the sclerotic areas of FSGS renal biopsy specimens. On the basis of their findings, following treatment of podocytes with transforming growth factor beta, lipopolysaccharide etc. in the presence or absence of glucocorticoids, found that glucocorticoids prevented downregulation of miR-30 (17).
Luo Y et al., demonstrated a 2.5-fold change in miRNA-30a-5p at enrollment, compared to controls (p=0.001). The values returned to normal after four weeks of steroid therapy. The triglycerides had a negative correlation. The miRNA expression was similar in the steroid-sensitive and steroid-resistant groups (11). Teng J et al., showed similar results in their group of patients with NS with significantly overexpressed miRNA-30a of 2.6-fold change in NS patients. The expression in the steroid-resistant was significantly higher than the steroid-sensitive NS (13). Zhang W et al., showed elevated urine miRNA-30a-5p excretion in patients with Focal Segmental Glomerulosclerosis (FSGS) (12). These authors screened several miRNAs of clinical interest by low-density microarray and validated each of them, including miRNA-30a-5p, by absolute quantification using RT-qPCR (11),(12),(13).
Limitation(s)
The present study was a preliminary study, to look into the trend of miRNA-30a-5p in children with steroid sensitive NS. The present study did not ascertain treatment response across various categories of NS.
The present study established an upregulation of miRNA-30a-5p in the children with steroid sensitive NS. The expression of miRNA-30a-5p was higher than in the control group. The study suggested that miRNA-30a-5p plays an essential role in the progression of NS and has the potential as a novel biomarker of childhood NS. Further studies on miRNA-30a-5p in NS are required, to explore the mechanism of its influence on NS and its pathological types.
DOI: 10.7860/JCDR/2023/59329.17683
Date of Submission: Jul 27, 2022
Date of Peer Review: Oct 27, 2022
Date of Acceptance: Dec 14, 2022
Date of Publishing: Mar 01, 2023
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA
PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jul 28, 2022
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• iThenticate Software: Dec 10, 2022 (9%)
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