Publications by authors named "Rajni Sharma"

242 Publications

The experiential impact of isolation and quarantine on patients during the initial phase of the COVID-19 pandemic in India.

Ind Psychiatry J 2020 Jul-Dec;29(2):310-316. Epub 2021 Mar 15.

Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Most countries around the world have been affected by the COVID-19 pandemic. Although there are quantitative studies on the effects of the COVID-19 pandemic on health-care professionals and other population groups, there are few studies that have evaluated the experiences of patients in the initial phases of the pandemic.

Aim: This study aims to conduct a qualitative study assessing the experiences of the patients in isolation and quarantine in the initial stage of the COVID-19 pandemic.

Methodology: The present study was a qualitative study through telephonic interviews with patients in isolation and quarantine due to COVID-19 from April 4 to 12, 2020. Patients in isolation had confirmed COVID-19 and were mandatorily admitted in specially designated COVID hospitals. Patients in quarantine were suspected to have COVID-19 due to symptoms or contact with confirmed patients with COVID-19.

Results: The experiences could be classified as having psychological impact, interpersonal impact, social impact, behavioral changes and impact on occupational aspects. The experience was predominantly unpleasant and characterized by anxiety, stigma, ostracization, guilt, and worry about the future.

Conclusion: The experiences of the individuals in both the groups emphasize the importance of addressing psychological stressors. It could be concluded that individuals and their families would accordingly benefit from effective interventions to deal with the negative experiences they have been through due to the present pandemic.
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http://dx.doi.org/10.4103/ipj.ipj_178_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188911PMC
March 2021

Soil Properties and Weed Dynamics in Wheat as Affected by Rice Residue Management in the Rice-Wheat Cropping System in South Asia: A Review.

Plants (Basel) 2021 May 10;10(5). Epub 2021 May 10.

Department of Soil Science, Punjab Agricultural University, Ludhiana 141004, India.

The rice-wheat cropping system (RWCS) has substantially contributed in making India self-sufficient in food grain production; however, rice residue management is of great concern, threatening the sustainability of this system. Rice residue is invariably disposed of by farmers through open burning. In addition to environmental pollution, residue burning of rice also leads to loss of soil nutrients. One of the alternatives to overcome these problems and sustain the RWCS is managing the rice residues in the field itself. Rice residue retention has variable effects on agricultural pests (namely, weeds, insect pests, diseases, and rodents) in the RWCS. High weed infestation in the RWCS results in high consumption of herbicides, which leads to several ecological problems and evolution of herbicide resistance. The shift from intensive tillage to conservation tillage causes major changes in weed dynamics and herbicide efficacy. Incorporation of rice residue reduces weed density and helps in improving soil physical, chemical, and biological properties. Rice residue retention on the surface or mulching reduces weed density and the biomass of both grass and broadleaf weeds in wheat crop as compared to its removal. Long-term field studies involving the use of rice residue as a component of integrated weed management strategies are needed to be done in the RWCS.
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http://dx.doi.org/10.3390/plants10050953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151931PMC
May 2021

Survival Outcomes of Newly Diagnosed Multiple Myeloma at a Tertiary Care Center in North India (IMAGe: 001A Study).

JCO Glob Oncol 2021 May;7:704-715

Army Hospital (RR), Delhi, India.

Purpose: The outcomes of patients with myeloma from developing countries are often lacking because of poor record maintenance. Publications from such settings are also limited because of the retrospective nature of the data collection. Information technology can bridge these gaps in developing countries with real-time data maintenance. We present the real-time survival data of the patients with myeloma from a tertiary care center in North India using one such indigenously built software.

Patients And Methods: These are real-time data of all patients with myeloma presenting to a tertiary care center from North India. The patient characteristics (demographics, baseline disease characteristics, risk stratification, and outcomes) were recorded contemporaneously. The survival of the study population was analyzed and grouped based on various disease characteristics at diagnosis.

Results: The median age of the study population (N = 696) was 65.9 (34.9-94.9) years with male predominance (65%). The median follow-up was 3.7 years (0-18.6 years) with the median overall survival (OS) not achieved. The OS of the study population at 1, 3, and 5 years was 94% (n = 558), 87.5% (n = 394), and 83.1% (n = 267), respectively. Most of the patients presented in advanced stages based on International Staging System (III:70%). On Kaplan-Meier analysis, the presence of weight loss ( = .01), renal dysfunction ( = .047), and anemia at diagnosis ( = .004) had a significant impact on survival. On Cox proportional model univariate analysis, the presence of renal dysfunction, anemia, and weight loss had the significant hazard ratio of 1.68 (1-2.82, = .049), 3.18 (1.39-7.29, = .0063), and 2.81 (1.22-6.42, = .014), respectively, whereas on multivariate analysis of hypercalcemia, renal disease, anemia, and bone disease (CRAB) features, only anemia was found to have a significant hazard ratio of 2.56 (1.01-6.47, = .046).

Conclusion: The real-world data show OS comparable with the published western literature. Only anemia was found to have significant impact on survival. The use of such software can aid in better data-keeping in resource-constrained settings.
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http://dx.doi.org/10.1200/GO.20.00625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162976PMC
May 2021

Renal gluconeogenesis in insulin resistance: A culprit for hyperglycemia in diabetes.

World J Diabetes 2021 May;12(5):556-568

Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.

Renal gluconeogenesis is one of the major pathways for endogenous glucose production. Impairment in this process may contribute to hyperglycemia in cases with insulin resistance and diabetes. We reviewed pertinent studies to elucidate the role of renal gluconeogenesis regulation in insulin resistance and diabetes. A consensus on the suppressive effect of insulin on kidney gluconeogenesis has started to build up. Insulin-resistant models exhibit reduced insulin receptor (IR) expression and/or post-receptor signaling in their kidney tissue. Reduced IR expression or post-receptor signaling can cause impairment in insulin's action on kidneys, which may increase renal gluconeogenesis in the state of insulin resistance. It is now established that the kidney contributes up to 20% of all glucose production gluconeogenesis in the post-absorptive phase. However, the rate of renal glucose release excessively increases in diabetes. The rise in renal glucose release in diabetes may contribute to fasting hyperglycemia and increased postprandial glucose levels. Enhanced glucose release by the kidneys and renal expression of the gluconeogenic-enzyme in diabetic rodents and humans further point towards the significance of renal gluconeogenesis. Overall, the available literature suggests that impairment in renal gluconeogenesis in an insulin-resistant state may contribute to hyperglycemia in type 2 diabetes.
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http://dx.doi.org/10.4239/wjd.v12.i5.556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107972PMC
May 2021

Diabetes Mellitus Due to Wolfram Syndrome Type 1 (DIDMOAD).

Indian Pediatr 2021 05;58(5):487-488

Department of Pediatrics, Division of Pediatric Endocrinology, All India Institute of Medical Sciences, New Delhi, India.

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May 2021

Long-term epilepsy control, motor function, cognition, sleep and quality of life in children with West syndrome.

Epilepsy Res 2021 Jul 2;173:106629. Epub 2021 Apr 2.

Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India. Electronic address:

Purpose: To assess epilepsy, motor function, cognitive, sleep, and quality of life outcomes and their predictors in a follow-up cohort with West syndrome (WS) at ≥5 years of age.

Methods: Cross-sectional evaluation in a follow-up cohort of WS (aged 5-14 years), between July 2018 and December 2019, was performed at a tertiary-care referral center in Northern India. 164 children were assessed in-person for epilepsy severity, functional status (gross motor and hand function), social quotient, behavioral comorbidities, sleep problems, and quality of life (QoL) using Early Childhood Epilepsy Severity Scale, Gross Motor Function Classification System, Manual Ability Classification System, Vineland Social Maturity Scale, Diagnostic and Statistical Manual of Mental disorders-5 criteria, Children's Sleep Habits Questionnaire, and PedsQL-Epilepsy module respectively. Furthermore, 238 children with the inability to visit the hospital were assessed through telephonic interview along with retrospective case record review for epilepsy control, gross and fine motor measures.

Results: 402 children with WS (75 % boys) with regular follow-up were studied and the majority (80 %) had underlying structural etiology. The median age (interquartile range) of the cohort was 92 (78-107) months. Of these, 60 % had evolved to Lennox-Gastaut syndrome (LGS). The following long-term outcomes were observed: ongoing epilepsy (261/402), unfavorable motor status (130/402), moderate to profound intellectual disability (111/164), autistic spectrum disorder (42/164), attention-deficit hyperactivity disorder (18/164), poor sleep (135/164), and impaired QoL (115/164). Non-structural etiology (odds ratio [OR] = 3.8, 95 % confidence interval [CI]: 2.1-5.5, p=<0·0001) and older age (>5 months) at the onset of epileptic spasms (OR = 2·9, 95 % CI: 1.5-5.0, p=<0·0001) were associated with enduring seizure freedom for more than two years.

Conclusion: The present study revealed a preponderance of structural etiology and a high rate of transition to LGS. Early age at onset of spasms (before five months) and structural etiology were the predictors of unfavorable long-term epilepsy outcome. QoL was impaired in more than two-thirds of patients and it correlated significantly with cognitive, sleep, motor, and behavioral outcomes. However, the results of our study should be interpreted in the context of significant attrition of the original cohort.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106629DOI Listing
July 2021

Nonalcoholic Fatty Liver Disease and Subclinical Hypothyroidism in Obese Children.

Authors:
Rajni Sharma

Indian J Pediatr 2021 05 2;88(5):425-426. Epub 2021 Apr 2.

Division of Pediatric Endocrinology, Room no. 3058, Teaching Block, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.

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http://dx.doi.org/10.1007/s12098-021-03749-xDOI Listing
May 2021

Gonadectomy in conditions affecting sex development: a registry-based cohort study.

Eur J Endocrinol 2021 May 4;184(6):791-801. Epub 2021 May 4.

Division of Paediatrics, University of Lübeck, Lübeck, Germany.

Objectives: To determine trends in clinical practice for individuals with DSD requiring gonadectomy.

Design: Retrospective cohort study.

Methods: Information regarding age at gonadectomy according to diagnosis; reported sex; time of presentation to specialist centre; and location of centre from cases reported to the International DSD Registry and who were over 16 years old in January 2019.

Results: Data regarding gonadectomy were available in 668 (88%) individuals from 44 centres. Of these, 248 (37%) (median age (range) 24 (17, 75) years) were male and 420 (63%) (median age (range) 26 (16, 86) years) were female. Gonadectomy was reported from 36 centres in 351/668 cases (53%). Females were more likely to undergo gonadectomy (n = 311, P < 0.0001). The indication for gonadectomy was reported in 268 (76%). The most common indication was mitigation of tumour risk in 172 (64%). Variations in the practice of gonadectomy were observed; of the 351 cases from 36 centres, 17 (5%) at 9 centres had undergone gonadectomy before their first presentation to the specialist centre. Median age at gonadectomy of cases from high-income countries and low-/middle-income countries (LMIC) was 13.0 years (0.1, 68) years and 16.5 years (1, 28), respectively (P < 0.0001) with the likelihood of long-term retention of gonads being higher in LMIC countries.

Conclusions: The likelihood of gonadectomy depends on the underlying diagnosis, sex of rearing and the geographical setting. Clinical benchmarks, which can be studied across all forms of DSD will allow a better understanding of the variation in the practice of gonadectomy.
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http://dx.doi.org/10.1530/EJE-20-1058DOI Listing
May 2021

Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India.

Front Immunol 2020 15;11:612323. Epub 2021 Jan 15.

Department of Pediatric Hematology Oncology and Bone Marrow Transplant, Kanchi Kamakoti Childs Trust Hospital, Chennai, India.

Background: There is paucity of literature on XLA from developing countries. Herein we report the clinical and molecular profile and outcome in a multicenter cohort of patients with XLA from India.

Methods: Data on XLA from all regional centers supported by the Foundation for Primary Immunodeficiency Diseases (FPID), USA and other institutions providing care to patients with PIDs were collated. Diagnosis of XLA was based on European Society for Immunodeficiencies (ESID) criteria.

Results: We received clinical details of 195 patients with a provisional diagnosis of XLA from 12 centers. At final analysis, 145 patients were included (137 'definite XLA' and eight 'probable/possible XLA'). Median age at onset of symptoms was 12.0 (6.0, 36.0) months and median age at diagnosis was 60.0 (31.5, 108) months. Pneumonia was the commonest clinical manifestation (82.6%) followed by otitis media (50%) and diarrhea (42%). Arthritis was seen in 26% patients while 23% patients developed meningitis. Bronchiectasis was seen in 10% and encephalitis (likely viral) in 4.8% patients. was the commonest bacterial pathogen identified followed by , and . Molecular analysis revealed 86 variants in 105 unrelated cases. Missense variants in gene were the most common (36%) followed by frameshift (22%) and nonsense variants (21%). Most pathogenic gene variants (53%) were clustered in the distal part of gene encompassing exons 14-19 encoding for the tyrosine kinase domain. Follow-up details were available for 108 patients. Of these, 12% had died till the time of this analysis. The 5-year and 10-year survival was 89.9% and 86.9% respectively. Median duration of follow-up was 61 months and total duration of follow-up was 6083.2 patient-months. All patients received intravenous immunoglobulin (IVIg) replacement therapy. However, in many patients IVIg could not be given at recommended doses or intervals due to difficulties in accessing this therapy because of financial reasons and lack of universal health insurance in India. Hematopoietic stem cell transplant was carried out in four (2.8%) patients.

Conclusion: There was a significant delay in the diagnosis and facilities for molecular diagnosis were not available at many centers. Optimal immunoglobulin replacement is still a challenge.
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http://dx.doi.org/10.3389/fimmu.2020.612323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873890PMC
June 2021

Psychological Morbidity among People in Quarantine.

J Neurosci Rural Pract 2021 Jan 29;12(1):67-70. Epub 2021 Jan 29.

Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

 This study aimed to evaluate psychological distress of persons in quarantine and compare the same with a group of persons, who are currently in lockdown.  Forty-four persons in quarantine and 45 subjects currently in lockdown were evaluated on Depression Anxiety Stress Scale II.  About three-fourth (77.3%) of the participants in the quarantine group and one-third (37.8%) in the comparator group had depression. About one fourth (22.7%) in the quarantine group and one-third (35.6%) in the lockdown group had anxiety.  The present study suggests that lockdown and being in quarantine are associated with significantly higher psychiatric morbidity, especially anxiety.
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http://dx.doi.org/10.1055/s-0040-1718855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846334PMC
January 2021

Feeling offended by clients: The experiences of doctoral student therapists.

J Couns Psychol 2021 Mar 5;68(2):125-138. Epub 2020 Nov 5.

Department of Psychology.

Ten doctoral student therapists (8 White, 5 female) in 1 counseling psychology doctoral program located in the Mid-Atlantic United States were interviewed for approximately 1 hour each about their experiences of feeling offended by a client during an individual psychotherapy session. Interview data were analyzed with consensual qualitative research (CQR). Trainee therapists typically felt offended related to their sociocultural identities (e.g., being a woman, LGBTQ+, racial-ethnic minority), felt frozen after the events and uncertain about how to respond, wished they had handled the events differently, and struggled when clients expressed opinions or beliefs that ran counter to their own values. Trainees had difficulty maintaining an empathic, nonjudgmental therapeutic stance where they could both value the client and maintain their own sense of integrity and beliefs about social justice and multiculturalism. Implications for training, practice, and research are provided. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/cou0000511DOI Listing
March 2021

Spectrum of Pathogenic Variants in SRD5A2 in Indian Children with 46,XY Disorders of Sex Development and Clinically Suspected Steroid 5α-Reductase 2 Deficiency.

Sex Dev 2019 5;13(5-6):228-239. Epub 2020 Sep 5.

The aim of this study was to assess the prevalence of pathogenic variants in the SRD5A2 gene in children with 46,XY disorders of sex development (DSD) with normal to high serum testosterone levels and absence of Müllerian structures on imaging and to evaluate the genotype-phenotype correlation. Seventy-five patients with 46,XY DSD and probable clinical diagnosis of 5α-reductase 2 deficiency or androgen insensitivity syndrome were enrolled. Genetic analysis was done for pathogenic variants in SRD5A2, and the genotype-phenotype correlation was studied. As a result, 10 pathogenic or likely pathogenic biallelic variants in SRD5A2, either homozygous or compound heterozygous, were identified in 25 of 75 (33.3%) patients. The hCG stimulated testosterone: dihydrotestosterone (T:DHT) ratio was elevated in all patients with pathogenic variants in SRD5A2 and in nearly 90% of those without pathogenic variants in SRD5A2 in whom this was assessed. The missense pathogenic variant p.R246Q was a hotspot. One novel pathogenic variant p.Y178*, and a variant p.F194I, not previously reported in patients with 5α-reductase 2 deficiency, were identified. The missense variant p.F194I was predicted as deleterious and damaging by in silico analysis and as likely to reduce the enzyme activity by protein modeling. In conclusion, pathogenic variants in SRD5A2 can be detected in a wide spectrum of Indian patients with 46,XY DSD. Molecular genetic analysis should be considered as a first-line test as the T:DHT ratio lacks specificity and a hotspot variant is present in a vast majority.
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http://dx.doi.org/10.1159/000509812DOI Listing
September 2020

Intestinal mucormycosis complicated by iliac artery aneurysm and ureteric rupture in a child with new-onset type 1 diabetes mellitus.

J Paediatr Child Health 2021 Jul 20;57(7):1117-1119. Epub 2020 Aug 20.

Division of Endocrinology and Diabetes, Medanta Medicity Hospital, Gurugram, India.

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http://dx.doi.org/10.1111/jpc.15126DOI Listing
July 2021

Medical nutrition therapy of pediatric type 1 diabetes mellitus in India: Unique aspects and challenges.

Pediatr Diabetes 2021 02 10;22(1):93-100. Epub 2020 Aug 10.

Department of Pediatrics, Nanavati Super Speciality Hospital, Mumbai, India.

Medical nutrition therapy (MNT) is a vital aspect of management of type 1 diabetes mellitus (T1DM) and should be tailored to ethnic and family traditions and the socioeconomic and educational status of the patient. In this article, we discuss the unique aspects of MNT in children and adolescents with T1DM in the Indian setting, with focus on the challenges faced by patients, dieticians and physicians and how these can be overcome. The authors reviewed the available literature on MNT in T1DM from India and prepared the document based on their vast collective clinical experience in treating patients with T1DM from different regions in India. Indian diets are predominantly carbohydrate-based with high glycemic index (GI) and low protein content. Various methods are available to increase the protein and fiber content and reduce the GI of food in order to limit glycemic excursions. Insulin regimens need to be tailored to the child's school timings, meal schedule, and the availability of a responsible adult to supervise/administer insulin. All patients, irrespective of economic and education background, should be taught the broad principles of healthy eating, balanced diet and carbohydrate counting. There are various barriers to dietary compliance, including joint family system, changing lifestyles, and other factors which need to be addressed. There is a need to customize dietary management according to patient characteristics and needs and develop standardized patient educational material on principles of healthy eating in various regional languages.
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http://dx.doi.org/10.1111/pedi.13080DOI Listing
February 2021

Accessing Counseling Services Where the Rainbow Doesn't Shine: A Heterosexism Audit Study.

J Homosex 2020 Mar 24:1-20. Epub 2020 Mar 24.

Department of Romance Languages and Linguistics, University of Vermont, Burlington, Vermont, USA.

Through a field experiment set among licensed therapists ( = 425), we found nuanced evidence of heterosexist discrimination at the entry point of mental health services for a fictitious White, presumably gay man seeking counseling. We called therapists in LGB-affirming and LGB-hostile states and left voicemails requesting services. To manipulate perceived sexual orientation, a confederate using the name "Jon" recorded one of three conditions (a) heterosexual-presenting Jon, (b) gay-presenting Jon, and (c) gay-sounding Jon. Analyzes comparing the rate of returned calls for each condition within LGB-affirming versus LGB-hostile states against our referent group, gay-presenting Jon calling mental health professionals in an LGB-affirming region, revealed a number of significant effects. Notably, being perceived as gay in LGB-hostile states significantly decreased the rate of returned calls, with the reverse being true in an LGB-affirming state. The use of "gay-sounding" voice, however, did not appreciably affect these relationships.
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http://dx.doi.org/10.1080/00918369.2020.1734377DOI Listing
March 2020

A novel spectrophotometric method for simultaneous estimation of dibenzothiophene and 2-hydroxybiphenyl in their mixed spectrum and its application in screening of specific biodesulfurizing microbes.

3 Biotech 2020 Apr 3;10(4):153. Epub 2020 Mar 3.

1Department of Biotechnology, Punjabi University, Patiala, Punjab 147002 India.

The desulfurization of fuel is currently enforced to meet environmental legislation and prevent pollution. The use of specific biodesulfurizing microbes with a unique 4S pathway allows the desulfurization without compromising the quality of fuel. These specific microbes can be screened by the detection of 2-hydroxybiphenol (2-HBP) in desulfurizing mixture of dibenzothiophene (DBT). At present, colorimetric Gibb's assay is the most commonly employed screening method which requires a specific reagent, i.e., 2,6-dichloroquninone-4-chloramide. In the present study, a novel and simple spectrophotometric method was developed for the detection of 2-HBP for screening purpose based on dual wavelength method. The developed method facilitates the simultaneous analysis of DBT desulfurization and 2-HBP production in a sample by merely measuring the absorbance differences at two specified wavelengths, i.e., Δ ( - ) for DBT and Δ ( - ) for 2-HBP. The developed method was used to screen 57 microbes and two specific desulfurizing microbes MS-5 and BR-31 were selected based on 2-HBP production. The outcomes of developed method were validated by HPLC analysis. The strains MS-5 and BR-31 were employed in biodesulfurization and resulted in 54.88 ± 1.12% and 55.72 ± 1.32% desulfurization of 1.0 mM DBT, respectively. The developed method for screening of specific desulfurizing microbes does not require any specific reagent or sophisticated instrument in spite of being quick and reliable. The microbes selected by developed method exhibited excellent potential for biodesulfurization of fuel.
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http://dx.doi.org/10.1007/s13205-020-2138-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054501PMC
April 2020

Management of Infants with Congenital Adrenal Hyperplasia.

Indian Pediatr 2020 02;57(2):159-164

Department of Pediatrics, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India. Correspondence to: Prof Sangeeta Yadav, Department of Pediatrics, Maulana Azad Medical College and Lok Nayak Hospital. New Delhi 110 002, India.

Treatment of congenital adrenal hyperplasia (CAH) requires lifelong replacement of glucocorticoids with regular follow up to manage associated morbidities. The current review focuses on follow-up and management of infants diagnosed with classical CAH pertinent to Indian context. Early initiation of oral hydrocortisone in divided doses is recommended after diagnosis in newborn period, infancy and childhood. Fludrocortisone is recommended for all infants with classical CAH. All infants should be monitored as per protocol for disease and treatment related complications. The role of prenatal steroids to pregnant women with previous history of CAH affected infant for prevention of virilization of female fetus is controversial.
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February 2020

Vital Need for Sex Education in Indian Youth and Adolescents.

Authors:
Rajni Sharma

Indian J Pediatr 2020 04 11;87(4):255. Epub 2020 Feb 11.

Division of Pediatric Endocrinology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1007/s12098-020-03240-zDOI Listing
April 2020

Phosphoenolpyruvate carboxykinase in urine exosomes reflect impairment in renal gluconeogenesis in early insulin resistance and diabetes.

Am J Physiol Renal Physiol 2020 03 10;318(3):F720-F731. Epub 2020 Feb 10.

Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Impaired insulin-induced suppression of renal gluconeogenesis could be a risk for hyperglycemia. Diabetes is associated with elevated renal gluconeogenesis; however, its regulation in early insulin resistance is unclear in humans. A noninvasive marker of renal gluconeogenesis would be helpful. Here, we show that human urine exosomes (uE) contain three gluconeogenic enzymes: phosphoenolpyruvate carboxykinase (PEPCK), fructose 1,6-bisphosphatase, and glucose 6-phosphatase. Their protein levels were positively associated with whole body insulin sensitivity. PEPCK protein in uE exhibited a meal-induced suppression. However, subjects with lower insulin sensitivity had blunted meal-induced suppression. Also, uE from subjects with prediabetes and diabetic rats had higher PEPCK relative to nondiabetic controls. Moreover, uE-PEPCK was higher in drug-naïve subjects with diabetes relative to drug-treated subjects with diabetes. To determine whether increased renal gluconeogenesis is associated with hyperglycemia or PEPCK expression in uE, acidosis was induced in rats by 0.28 M NHCl with 0.5% sucrose in drinking water. Control rats were maintained on 0.5% sucrose. At the seventh day posttreatment, gluconeogenic enzyme activity in the kidneys, but not in the liver, was higher in acidotic rats. These rats had elevated PEPCK in their uE and a significant rise in blood glucose relative to controls. The induction of gluconeogenesis in human proximal tubule cells increased PEPCK expression in both human proximal tubules and human proximal tubule-secreted exosomes in the media. Overall, gluconeogenic enzymes are detectable in human uE. Elevated PEPCK and its blunted meal-induced suppression in human urine exosomes are associated with diabetes and early insulin resistance.
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http://dx.doi.org/10.1152/ajprenal.00507.2019DOI Listing
March 2020

Immune checkpoint status and tumor microenvironment in vulvar squamous cell carcinoma.

Virchows Arch 2020 Jul 28;477(1):93-102. Epub 2020 Jan 28.

Department of Pathology, The University of Alabama at Birmingham, West Pavilion P210, 619 19th Street, South Birmingham, AL, 35249-7331, USA.

Vulvar squamous cell carcinoma accounts for 5% of cancers of the female genital tract. Current guidelines recommend wide local excision with negative surgical margins as the standard treatment. However, the extent of the tumor-free resection margin after wide local excision is still controversial in many cases. Drugs targeting immune checkpoints such as PD-1 or its ligand PD-L1 have potential clinical utility in these patients. We examined the expression of PD-L1 in tumor cells and immune cells, as well as the proportion of PD-1, CD8, and FOXP3 positive lymphocytes. Twenty-one cases of invasive vulvar squamous cell carcinomas were reviewed. Whole slides of representative formalin-fixed, paraffin-embedded archival material were used for analysis. Odds ratios (OR) and hazard ratios (HR) were used to estimate risk for disease recurrence, overall mortality, and cancer mortality. PD-L1 expression was found in 43% of tumor cells, with higher proportions in intratumoral (67%) and peritumoral (81%) immune cells. OR and HR for disease recurrence and cancer mortality were higher in tumors with higher CD8 expression. OR and HR for overall mortality were also higher in tumors with higher PD-L1 and CD8 expression. In conclusion, nearly half of cases were PD-L1 positive in tumor cells with over two-third of cases demonstrating PD-L1 positivity in immune cells. Immunohistochemical expression of PD-L1 and CD8 could be used to suggest higher risk of disease recurrence, overall mortality, and cancer mortality. Furthermore, our data contributes to the growing evidence that targeting the PD-1/PD-L1 pathway may be beneficial in vulvar squamous cell carcinomas.
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http://dx.doi.org/10.1007/s00428-020-02759-yDOI Listing
July 2020

Newborn Screening and Diagnosis of Infants with Congenital Adrenal Hyperplasia.

Indian Pediatr 2020 01;57(1):49-55

Department of Pediatrics, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India. Correspondence to: Dr Seema Kapoor, Director Professor, Department of Pediatrics, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive endocrine disorder which can manifest after birth with ambiguous genitalia and salt-wasting crisis. However, genital ambiguity is not seen in male babies and may be mild in female babies, leading to a missed diagnosis of classical CAH at birth. In this review, we provide a standard operating protocol for routine newborn screening for CAH in Indian settings. A standardization of first tier screening tests with a single consistent set of cut-off values stratified by gestational age is also suggested. The protocol also recommends a two-tier protocol of initial immunoassay/time resolved fluoroimmunoassay followed by liquid chromatography tandem mass spectrometry for confirmation of screen positive babies, wherever feasible. Routine molecular and genetic testing is not essential for establishing the diagnosis in all screen positive babies, but has significant utility in prenatal diagnosis and genetic counseling for future pregnancy.
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January 2020

Quality of life, adjustment, and associative comorbid conditions in children diagnosed with attention deficit hyperactivity disorder: A comparative study.

Ind Psychiatry J 2020 Jan-Jun;29(1):123-129. Epub 2020 Nov 7.

Department of Psychiatry, PGIMER, Chandigarh, India.

Introduction: Attention deficit hyperactivity disorder (ADHD) is a common pediatric, neurodevelopmental disorder, with serious impacts on lives of those suffering from it. ADHD is known to be associated with social and emotional difficulties, poor self-regulation, aggression, reduced empathy, inability to regulate socially desirable behavior along with conflicts within family, and increased conflict with peers and several associated comorbid conditions.

Aim: The study aims at exploring quality of life (QOL) and adjustment along with associated comorbid conditions in children diagnosed with ADHD in comparison with normal children.

Methods: A total sample of 60 children including 30 children diagnosed with ADHD and 30 normal children were selected and assessed using Vanderbilt ADHD Parent rating scale Childhood Psychopathology Measurement Schedule, KINDL QOL: Parent Questionnaire and Pre-Adolescent adjustment Scale to assess level of ADHD, comorbid psychopathologies, their QOL and adjustment respectively.

Results: Overall results have indicated that parents reported lesser symptom and pathology in comparisons to teachers for ADHD. Those diagnosed with ADHD had positive and significant comorbidities associated of; low intelligence with behavioral problems and high levels of conduct problems, anxiety, depression, psychotic tendencies, physical illness with emotional problems and somatization in comparison to normal and thus a poor adjusted life, with significant report of poor self-esteem and peer relations and QOL.

Conclusion: The results of the present study has clearly stated that severe burden has been perceived by ADHD children, with a poor perceived QOL, several adjustment issues, and sufferance of one or other comorbidity. Thus, the study could help understand and emphasize the need of holistic treatment comprising medicinal and therapeutic methods, including intervention for parents, focusing exclusively on enhancing and curbing these factors.
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http://dx.doi.org/10.4103/ipj.ipj_119_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989465PMC
November 2020

Immunogenicity and Protective Efficacy of Seasonal Human Live Attenuated Cold-Adapted Influenza Virus Vaccine in Pigs.

Front Immunol 2019 8;10:2625. Epub 2019 Nov 8.

Enhanced Host Responses, The Pirbright Institute, Woking, United Kingdom.

Influenza A virus infection is a global health threat to livestock and humans, causing substantial mortality and morbidity. As both pigs and humans are readily infected with influenza viruses of similar subtype, the pig is a robust and appropriate model for investigating swine and human disease. We evaluated the efficacy of the human cold-adapted 2017-2018 quadrivalent seasonal LAIV in pigs against H1N1pdm09 challenge. LAIV immunized animals showed significantly reduced viral load in nasal swabs. There was limited replication of the H1N1 component of the vaccine in the nose, a limited response to H1N1 in the lung lymph nodes and a low H1N1 serum neutralizing titer. In contrast there was better replication of the H3N2 component of the LAIV, accompanied by a stronger response to H3N2 in the tracheobronchial lymph nodes (TBLN). Our data demonstrates that a single administration of human quadrivalent LAIV shows limited replication in the nose and induces detectable responses to the H1N1 and H3N2 components. These data suggest that pigs may be a useful model for assessing LAIV against influenza A viruses.
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http://dx.doi.org/10.3389/fimmu.2019.02625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856147PMC
November 2020

Life-threatening Hypercalcemia as the First Manifestation of Acute Lymphoblastic Leukemia.

Indian Pediatr 2019 11;56(11):972-974

Department of Pediatrics, AIIMS, New Delhi, India.

Hypercalcemia of malignancy, usually reported in adults in advanced stages, is rare in children. A 4-year-old boy presented with intermittent episodes of severe hypercalcemia, which improved with intravenous hydration therapy, furosemide and bisphosphonates as the initial manifestation of occult acute lymphoblastic leukemia. Pediatricians should rule out hematological malignancy in patients with severe hypercalcemia.
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November 2019

Use of Smartphone Applications in Children with Type 1 Diabetes Mellitus.

Authors:
Rajni Sharma

Indian J Pediatr 2019 12 11;86(12):1087-1088. Epub 2019 Nov 11.

Division of Pediatric Endocrinology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.

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http://dx.doi.org/10.1007/s12098-019-03108-xDOI Listing
December 2019

Diffuse normolipemic plane xanthoma with underlying photosensitive dermatoses.

BMJ Case Rep 2019 Nov 2;12(11). Epub 2019 Nov 2.

Surgery, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India

Diffuse plane xanthomatosis is a normolipemic non-Langerhan cell histiocytosis. Clinically, patient presents as asymptomatic yellowish plaques involving eyelids, neck, upper trunk and flexures. Usually, there is an associated haematological or lymphoproliferative malignancy which may precede or follow dermatological manifestations by many years. Rarely inflammatory dermatosis like atopic eczema, photosensitive dermatosis, erythroderma, previous scars and lymphoedema have been found to be associated with these xanthomas. We are reporting a 46-year-old male patient who had a history of photosensitivity for the last 15 years and subsequently developed diffuse plane normolipemic xanthomas.
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http://dx.doi.org/10.1136/bcr-2019-230720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827770PMC
November 2019

To study the profile of isolates and antifungal susceptibility pattern of neonatal sepsis in a tertiary care hospital of North India.

J Matern Fetal Neonatal Med 2021 Aug 3;34(16):2655-2659. Epub 2019 Oct 3.

Mahatma Gandhi National Institute of Medical Sciences, Jaipur, India.

Aims And Objective: To study the profile of infection and antifungal susceptibility (AFS) pattern in neonatal sepsis.

Materials And Methods: In this prospective observational study, 850 blood samples were collected and processed from neonates who were suspected clinically to have sepsis. The blood culture that showed growth of was further processed for species identification. Antifungal susceptibility was done as per the National Committee for Clinical Laboratory Standards (NCCLS)/Clinical Laboratory Standards Institute (CLSI) M44-A-2 guidelines by disc diffusion method and automated vitek-2 compact system. Candidemia was diagnosed by isolation of species from at least one positive blood culture containing pure growth of species with supportive clinical features.

Results: species were isolated in 32 specimens of the total 322 culture-positive cases. The most common isolate was (14/32; 43.75%) followed by (7/32; 21.87%) and (6/32; 18.75%). The three most common neonatal risk factors for candidemia were low birth weight, prolonged use of intravenous antibiotics and presence of central venous line. Non- (NAC) showed good sensitivity to fluconazole as compared to . The fluconazole sensitivity of , , and was 93, 67, and 100%, respectively, whereas it was 57% in . The sensitivity to amphotericin B was 95% among all isolates. All NAC were sensitive to amphotericin B, while only 72% were sensitive to amphotericin B.

Conclusions: The incidence of neonatal sepsis secondary to NAC is increasing and has replaced as a major cause of neonatal fungal sepsis. Low birth weight is the most important risk factor for sepsis. The resistance of is increasing for both fluconazole and amphotericin B when compared to NAC. Increasing antifungal resistance warrants its judicious use both for prophylaxis and treatment.
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http://dx.doi.org/10.1080/14767058.2019.1670799DOI Listing
August 2021

Tumour immune microenvironment in primary and metastatic papillary renal cell carcinoma.

Histopathology 2020 Feb 11;76(3):423-432. Epub 2019 Dec 11.

Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.

Aims: Among renal cell carcinoma (RCC) the tumour immune microenvironment has been best characterised in clear cell RCC. In this study we investigated the expression of several immune markers, including PD-L1, FoxP3 and CD8 in primary and metastatic papillary RCC.

Methods And Results: Three tissue microarrays were constructed from 78 cases with primary papillary RCC and paired metastatic tumour (24 cases) from 78 patients treated between 1982 and 2014. Immunohistochemistry analysis was performed using commercially available antibodies for PD-L1 (clone E1L3N), FoxP3, CD8 and Ki-67. Markers expression level in tumour and/or associated immune cells was analysed by tissue type (non-tumour versus primary tumour versus metastatic tumour) and correlated to clinicopathological features and outcome.

Conclusion: We found PD-L1 expression in up to one-quarter of primary and metastatic papillary RCC. On univariate analysis, CD8/FoxP3 ratio >1 was associated with favourable outcome, whereas papillary RCCs with high numbers of dual CD8/Ki-67-positive lymphocytes showed an increased likelihood for tumour progression and overall and cancer-related mortality. The association of CD8/FoxP3 ratio >1 and high count of CD8/Ki-67 with outcome remained significant on multivariate analysis when adjusting for stage, grade and patient's age.
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http://dx.doi.org/10.1111/his.13987DOI Listing
February 2020

Khellinoflavanone, a Semisynthetic Derivative of Khellin, Overcomes Benzo[]pyrene Toxicity in Human Normal and Cancer Cells That Express CYP1A1.

ACS Omega 2018 Aug 1;3(8):8553-8566. Epub 2018 Aug 1.

Natural Products Chemistry Division, Academy of Scientific & Innovative Research, and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.

Cytochrome P450 family 1 (CYP1) enzymes catalyze the metabolic activation of environmental procarcinogens such as benzo[]pyrene, B[]P, into carcinogens, which initiates the process of carcinogenesis. Thus, stopping the metabolic activation of procarcinogens can possibly prevent the onset of cancer. Several natural products have been reported to show unique ability in inhibiting CYP1 enzymes. We found that khellin, a naturally occurring furanochromone from , inhibits CYP1A1 enzyme with an IC value of 4.02 μM in CYP1A1-overexpressing human HEK293 suspension cells. To further explore this natural product for discovery of more potent and selective CYP1A1 inhibitors, two sets of semisynthetic derivatives were prepared. Treatment of khellin with alkali results in opening of a pyrone ring, yielding khellinone (). Claisen-Schmidt condensation of khellinone () with various aldehydes in presence of potassium hydroxide, at room temperature, provides a series of furanochalcones (khellinochalcones). Treatment of khellinone () with aryl aldehydes in the presence of piperidine, under reflux, affords the flavanone series of compounds (khellinoflavanones). The khellinoflavanone potently inhibited CYP1A1 with an IC value of 140 nM in live cells, with 170-fold selectivity over CYP1B1 (IC for CYP1B1 = 23.8 μM). Compound at 3× IC concentration for inhibition of CYP1A1 completely protected HEK293 cells from CYP1A1-mediated B[]P toxicity. Lung cancer cells, A549 (p53) and Calu-1 (p53-null), blocked in growth at the S-phase by B[]P were restored into the cell cycle by compound . The results presented herein strongly indicate the potential of these khellin derivatives for further development as cancer chemopreventive agents.
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http://dx.doi.org/10.1021/acsomega.8b01088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645225PMC
August 2018

X-Linked ALG13 Gene Variant as a Cause of Epileptic Encephalopathy in Girls.

Indian J Pediatr 2019 11 23;86(11):1072-1073. Epub 2019 Aug 23.

Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

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http://dx.doi.org/10.1007/s12098-019-03059-3DOI Listing
November 2019