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To define the spectrum of genetic disorders in patients with short stature visiting the genetic out-patient department in a tertiary care hospital.A chart review was done for 455 individuals (10 months-16 yrs) with short stature, who were evaluated at the genetic clinic from 1 January, 2017 upto 31 October, 2018. 226 patients who needed detailed evaluation, the spectrum of genetic diagnosis is presented.Proportionate short stature was identified in 63% individuals (n=142) of which 93 (65%) were recognizable syndromes such as Turner syndrome, and William syndrome, and RASopathies. In clinically undefined syndromes (39, 27%), a diagnosis could be made by karyotype (n=3/10), chromosomal microarray (6/12) and exome sequencing (1/6). In the 84 children in the disproportionate short stature group (37%), lysosomal storage disorders (LSDs) (45%, n=38) were identified by enzyme analysis in 86.8% and skeletal dysplasias (44%, n=37) identified by skeletal survey in 89% cases.In undefined syndromic short stature, chromosomal microarray may be the first investigation of choice if phenotyping is not suggestive of a specific genetic syndrome. Exome sequencing can be useful in identifying newer genes among idiopathic and familial short stature cohorts.

With the inception of the Internet of Things (IoT), wireless technology found a new outlook where the physical objects can interact with each other and can sense the environment. The IoT has found its way in the real world and has connected billions of devices throughout the world. However, its limitations, such as limited processing capability, storage capability, security and privacy issues, and energy constraints prevent the IoT system to be properly utilized by the real-world applications. Hence, the integration of IoT with various emerging technologies like big data, software defined networks, machine learning, fog computing, sensor cloud, etc., will make the IoT system a more powerful technology. The sensor cloud provides an open, secure, flexible, large storage and a computational capable infrastructure which makes the ensemble architecture of IoT and sensor cloud more efficient. An extensive review of the IoT system enabled sensor cloud is presented in the paper, and with this context, the paper attempts to summarize the sensor cloud infrastructure along with its challenges. In addition, the paper presents the possible integrated architecture of the IoT and the sensor cloud which enables the network to be properly utilized. Further, the importance of integrating these two promising technologies and research challenges associated with it is also identified. Finally, the paper analyses and discusses the motivation behind the ensemble system along with future research direction.

Background & Aims Lysosomal storage disorders (LSDs) remain a significant cause of morbidity in the Indian population and treatment is largely out of reach for most patients. Although data on enzymatic and molecular diagnosis of Gaucher disease (GD) and Fabry disease (FD) in Indian patients are available, the present study intended to establish the pathogenic levels of Lyso GL-1 and Lyso GL-3 in patients of GD and FD respectively as diagnostic aids. Materials and Methods From 2017 to 2019, ninety confirmed Gaucher cases (by enzymatic and molecular analysis) were tested for chitotriosidase (fluorometrically) and Lyso GL-1 (LC-MS/MS) and ten confirmed Fabry cases were analyzed for Lyso GL-3 (LC-MS/MS). Results Lyso GL-1 (median: 685.5 ng/mL, cut-off: 14) and Lyso GL-3 (median: 75.6 ng/mL, cut-off: 3.5) were found to be elevated in all enzymatically deficient patients of GD and FD respectively, however, no specific trend was observed between the levels of these biomarkers and the pathogenic variant(s) present in the patients of these disorders. Conclusions This is the first report on Lyso GL-1 and Lyso GL-3 levels in Indian patients of GD and FD respectively. These results will be useful for early diagnosis to improve management of these LSDs.

Happiness is a key to success. Being happy is a state of mind in the true sense when a person is mentally present at a place and sounds happy from within. It is observed that a happy person can solve many difficult problems in a couple of minutes. So, it will not be wrong to say that happiness is positivity because when a person is happy he is loaded with an enormous amount of energy which keeps him motivated. Every person passes through different stages of development; infancy, childhood, adolescence, youth, adulthood, and old age in which each stage has its own sweet as well as sour memories, but over time from infancy to childhood and then to adolescence almost everyone changes and is loaded with responsibilities. With time everything changes are its people, place, situation, society, technology, science, environment and the emergence of COVID-19 (coronavirus disease) is an infectious disease caused by a newly discovered coronavirus, has proved it to be right that people have to modify themselves with the changing situations. This COVID-19 has also proved Charles Darwin’s concept the right that says “survival of the fittest”, meaning a fit person will only survive and the unhealthy will be eliminated. COVID-19 being a pandemic disease have scattered everything be it people’s life (emotions, state of mind, jobs, education, economic state, relationships, family, etc.), the economic crisis has occurred in overall all states, railways/airlines services have stopped, for instance, one can feel the sudden full stop to almost all the present essential services.

Remembering my childhood days when I used to enjoy my summer and winter vacations with my maternal grandparents and those were one of the best memories of my life which are unforgettable. We all family members have a lot of fun, joy, and happiness with each other and my grandma used to narrate us beautiful stories; which cannot ever be replaced with today‟s era of technology. Family is the pillar in building up a child, where elements of love, care, feel, security, trust, are the building blocks. Family is the first place of socialization for a child where he/she learns culture, moral values, traditions, customs, etiquettes, and behaviour which gives a child a life direction. There are different types of family structure in our Indian society nuclear, joint and extended family in these every epoch has their own true stories in which they have enjoyed a lot and has their wonderful flashback memories and at the time when they don‟t have any social media or smartphone but they all are very excited, full of life, enjoyable, hard-working and living to the fullest. On contrary, when coming to network society children just loves social media from starting of the day till a good night virtual message is the most essential task of today‟s generation which they feel is their world where they have hundreds of virtual friends but no one to share their thoughts and feelings which makes them feel isolated from others, depressed and lost, frustrated and low when they are said to do anything and emotionless because they are lost in their own virtual world.Keywords: family, culture, social media, nuclear family, virtual life.

We evaluated the clinical histories, motor and pulmonary functions, cardiac phenotypes and GAA genotypes of an Indian cohort of twenty patients with late onset Pompe disease (LOPD) in this multi-centre study. A mean age at onset of symptoms and diagnosis of 9.9 ±9.7 years and 15.8 ±12.1 years respectively was identified. All patients had lower extremity limb-girdle muscle weakness. Seven required ventilatory support and seven used mobility assists. Of the four who used both assists, two received ventilatory support prior to wheelchair use. Cardiac involvement was seen in eight patients with various combinations of left ventricular hypertrophy, tricuspid regurgitation, cardiomyopathy,dilated ventricles with biventricular dysfunction and aortic regurgitation. Amongst 20 biochemically diagnosed patients (low residual GAA enzyme activity) GAA genotypes of 19 patients identified homozygous variants in eight and compound heterozygous in 11: 27 missense, 3 nonsense, 2 initiator codon, 3 splice site and one deletion. Nine variants in 7 patients were novel. The leaky Caucasian, splice site LOPD variant, c. −32 −13T > G mutation was absent. This first study from India provides an insight into a more severe LOPD phenotype with earlier disease onset at 9.9 years compared to 33.3 years in Caucasian patients, and cardiac involvement more than previously reported. The need for improvement in awareness and diagnosis of LOPD in India is highlighted

Background: Late onset Pompe disease (LOPD) is rare and generally manifests predominantly as progressive limb girdle muscle weakness. It is linked to the pathogenic mutations in GAA gene, which leads to glycogen accumulation in various tissues. Materials and methods: We describe the unusual clinical, biochemical, histopathological and genetic characteristics of 5 cases of LOPD. Results: The first case had progressive anterior horn cell like disease (AHCD) that evolved later to classical limb girdle syndrome and respiratory failure, the second patient had rigid spine syndrome with gastrointestinal manifestations, the third had limb girdle weakness superimposed with episodic prolonged worsening and respiratory failure, the fourth had large fibre sensory neuropathy without primary muscle involvement and the fifth presented with classical limb girdle muscle weakness. Two homozygous missense mutations c.1461C > A (p.Phe487Leu) and c.1082C > T (p.Pro361Leu) in the GAA gene were identified in case 1 and 2 respectively. Case 3 was compound heterozygous with inframe c.1935_1940del (p.Val646_Cys647del) and an intronic splice effecting variant c.-32-13T > G. Compound heterozygous missense variants c.971C > T (p.Pro324Leu) and c.794G > A (p.Ser265Asn) were identified in case 4. Case 5 had a frameshift insertion c.1396dupG (p.Val466GlyfsTer40) and a synonymous splice affecting variant c.546G > T(p.Thr182=). Conclusion: We are describing for the first time from India on LOPD with unusual phenotypes identified. A high degree of clinical suspicion and diagnosing rare phenotypes of Pompe disease is imperative to consider early initiation of Enzyme Replacement Therapy (ERT).

Newborn screening (NBS) aims toward early detection of treatable congenital disorders. From January 2008 through December 2017, 13,376 newborns were screened for congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), and glucose-6-phosphate dehydrogenase (G6PD) deficiency at Sir Ganga Ram Hospital, India, by measuring G6PD activity, thyroid-stimulating hormone, and 17-hydroxyprogesterone on dried blood specimens. The birth prevalence of 1:2,000 for CH, 1:2,500 for CAH, and 1:125 for G6PD deficiency indicates the latter as the most prevalent. Performance evaluation of testing reveals a robust screening program with 100% sensitivity and >99% specificity. Hence, we recommend NBS for early diagnosis and treatment to prevent adverse outcomes.

The most widespread notion of mobility model is the representation of mobile node’s movement pattern in the wireless ad hoc networks which has a significant impact on the performance of the network protocols. In this paper, we have proposed an Animal Migration Inspired Group Mobility (AMIGM) model for mobile ad hoc networks based on the migration behavior of animals like, insects, flock of birds, schools of fishes, reptiles, amphibians, etc. The propound model tries to overcome the limitations of the existing mobility models, such as temporal dependencies, spatial dependencies, geographical restrictions and migration of nodes between the group of nodes so that it can realistically model the real world application scenarios. The proposed AMIGM model is based on Animal Migration Optimization (AMO) algorithm, in which each group of nodes has two phases namely, Migration phase and Population updating phase. In the first phase, the model simulates the movement of nodes in the group from one position to another by obeying the swarming laws. In the second phase, the model simulates joining and leaving of the nodes in the group during migration. The protocol dependent and independent performance metrics of the proposed model are compared with Random Waypoint Mobility model (RWP) and Reference Point Group Mobility model (RPGM) through ns-2 simulator.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) accounts for 2.6% of the patients with chronic kidney disease in India. ADPKD is caused by pathogenic variants in either PKD1 or PKD2 gene. There is no comprehensive genetic data from Indian subcontinent. We aimed to identify the pathogenic variants in the heterogeneous Indian population. PKD1 and PKD2 variants were identified by direct gene sequencing and/or multiplex ligation-dependent probe amplification (MLPA) in 125 unrelated patients of ADPKD. The pathogenic potential of the variants was evaluated computationally and were classified according to ACMG guidelines. Overall 300 variants were observed in PKD1 and PKD2 genes, of which 141 (47%) have been reported previously as benign. The remaining 159 variants were categorized into different classes based on their pathogenicity. Pathogenic variants were observed in 105 (84%) of 125 patients, of which 99 (94.3%) were linked to PKD1 gene and 6 (6.1%) to PKD2 gene. Of 159 variants, 97 were novel variants, of which 43 (44.33%) were pathogenic, and 10 (10.31%) were of uncertain significance. Our data demonstrate the diverse genotypic makeup of single gene disorders in India as compared to the West. These data would be valuable in counseling and further identification of probable donors among the relatives of patients with ADPKD.

Objectives Diagnosis of lysosomal storage disorders (LSDs) remains challenging due to wide clinical, biochemical and molecular heterogeneity. The study applies a combined biochemical and genetic approach to diagnose symptomatic Indian patients of Pompe, Fabry, Gaucher and Hurler disease to generate a comprehensive dataset of pathogenic variants for these disorders. Design & methods Symptomatic patients were biochemically diagnosed by fluorometric methods and molecular confirmation was carried out by gene sequencing. Genetic variants were analyzed according to the ACMG/AMP 2015 variant interpretation guidelines. Results Amongst the 2181 suspected patients, 285 (13%) were biochemically diagnosed. Of these, 22.5% (64/285) diagnosed with Pompe disease harboured c.1933G>A, c.1A>G, c.1927G>A and c.2783G>C as common and 10 novel pathogenic variants while 7.4% (21/285) patients diagnosed with Fabry disease carried c.851T>C, c.902G>A, c.905A>C and c.1212_1234del as frequent disease-causing variants along with 7 novel pathogenic variants. As many as 48.4% (138/285) patients were diagnosed with Gaucher disease and had c.1448T>C as the most common pathogenic variant followed by c.1342G>C and c.754T>C with 7 previously unreported disease-causing variants and in the 21.7% (62/285) diagnosed cases of Hurler disease, c.1469T>C, c.754delC c.568_581del and c.1898C>T were identified as the most common causative variants along with 21 novel pathogenic variants. Conclusion This comprehensive data set of disease-causing frequent and novel pathogenic variants reported for the first time in such a large patient cohort for each of these four LSDs from the Indian sub-continent, along with their biochemical and clinical spectrum will contribute towards providing definitive diagnosis and treatment, identifying carrier status, as well as in counselling prenatal cases to reduce the morbidity and mortality associated with these disorders.

Background Prevention of genetic disorders in the family is gaining significance because of the burden of these untreatable and devastating disorders. Sir Ganga Ram Hospital (SGRH) has been at the forefront for prenatal diagnosis (PND) in India for the last 2 decades. Aims and objectives Evaluation of pregnant women for prenatal diagnosis in year 2017, and comparison with the centre's historical 5-year data published in 2003. Material and methods Pregnant women attending genetic clinics at SGRH and prenatal samples received from elsewhere were enrolled. Cytogenetic, molecular, biochemical and non-invasive methods were utilized for PND. Results Among 3351 pregnant women from SGRH, 2530 presented with obstetric indications, and 821 women had a background family history. In cytogenetic laboratory, 706 prenatal samples from SGRH and 553 samples from elsewhere were analyzed. Additional 623 women opted for Non-invasive prenatal test (NIPT) for aneuploidies. In molecular genetics laboratory, 733 prenatal samples were analyzed. Highlights in the study included the introduction of NIPT, and other major advances - chromosomal microarrays and next-generation sequencing enabling PND in 130 and 20 cases, respectively. NIPT detected 10 cases of aneuploidy, with 10% false positivity in 623 women. Comparison with 5-year data from SGRH revealed a 6–10 fold rise in number of PNDs being performed, and addition of newer indications, materialized by newer methods of NGS and CMAs. Conclusion Advanced genetic testing methodologies like NIPT, NGS and CMA are rapidly changing the scenario of prenatal diagnosis in our country, which is reflected in our data of last one year.

Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G > A (p.Arg157His) and c.1168G > A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies. Electronic supplementary material The online version of this article (10.1186/s13023-018-0908-1) contains supplementary material, which is available to authorized users.

This paper propounds a novel Biogeography Inspired Group Mobility model for Mobile Ad Hoc Networks (MANETs) based on the Biogeography Based Optimization (BBO) algorithm. BBO describes the migration behavior of species between the islands and how they become extinct and new species arise. Many mobility models present in the literature failed to realistically represent the movement of nodes within the group and migration of nodes from one group to another group. To address these issues, each group of nodes in the proposed mobility model follows the bird flocking rules; inspired from the movement of flock of birds. These nodes then migrate from one group to another group based on BBO approach, showing group mobility behavior among the group of nodes in MANETs which exhibit frequent group motion and network topology changes. The experimental results obtained through ns-2 simulator is compared with a Random Waypoint Mobility model and Reference Point Group Mobility model and evaluated their network performance under different routing protocols.

Introduction Genetic modifying factors play a significant role in disease progression in autosomal dominant polycystic kidney disease (ADPKD). Identification of these factors could inform about targets for intervention. The present study investigates the role of Glu298Asp (c.894G > T) polymorphism of NOS3 gene in the progression of disease in ADPKD patients from North India, and compares with the results in studies among other ethnic groups. Methods Genotyping for c.894G > T polymorphism was carried out in 123 patients of ADPKD and 100 healthy controls using polymerase chain reaction method. The allelic and genotypic frequencies of patients of ADPKD and healthy controls were analyzed using Chi-Square test. The mean age at onset of ESRD in the patients with PKD1 gene mutations, and in those with hypertension was correlated with G and T alleles of this polymorphism using Student's t-test. Results Distribution of GG, GT and TT genotypes were 0.73, 0.25 and 0.02 in patients of ADPKD and 0.67, 0.31 and 0.02 in healthy controls, respectively. The differences in the genotype frequencies between patients and controls were not significant (p = 0.604). The frequency of mutant allele T of c.894G > T polymorphism did not vary significantly among patients of ADPKD with ESRD and those without ESRD (p = 0.112). This polymorphism was also not associated with hypertension (p = 0.681) and severity of disease in PKD1-linked patients (p = 0.582). Conclusions The GT/TT genotype of c.894G > T (Glu298Asp) polymorphism did not have a significant role in modifying the progression of the disease in patients of ADPKD, or those with mutations in PKD1 gene from North India.

Objective: To determine the diagnostic accuracy of preeclampsia (PE) screening test offered in early pregnancy for the prediction of the risks for early-onset (requiring delivery

Software Defined Networks (SDN) has been emerging as the new promising paradigm for the large scale, complex wireless ad hoc networks which separate the control plane from the data plane. Unfortunately, existing Mobile Ad hoc network architecture lacks the flexibility to monitor and control the data flow in the network. This paper presents a prototype of Software Defined MANETs (SDM) architecture describing the mobility pattern of the nodes in the network by offering a feasible, dynamic programmable network infrastructure. In addition, some existing mobility models on software defined MANETs are also simulated with Mininet.

Objective To offer accurate prenatal diagnosis of lysosomal storage disorders in early pregnancy. Method Prenatal enzymatic diagnoses of Gaucher, Fabry, Pompe, Niemann Pick A/B, Tay Sach, Sandoff, GM1, mucoplysaccharidoses, Wolman, Krabbe, Metachromatic leukodystrophy and Batten diseases were made in uncultured chorionic villi samples by fluorometric/spectrophotometric methods. Results Of 331 prenatal enzymatic diagnosis, 207 fetuses (67%) were normal and 124 (37%) were affected. The interpretation of affected, normal and carrier fetuses was done using their respective reference ranges as well as % enzyme activity of normal mean. The prenatal molecular confirmation was feasible in 43 biochemically diagnosed fetuses. Of the 207 normal reported fetuses, post natal enzymatic confirmation was done in 23 babies, clinical status of another 165 babies was assessed as unaffected via questionnaire on telephone and 19 were lost to follow-up. In affected pregnancies, 123 opted for termination of which 44 were confirmed enzymatically after abortion. A single false positive was determined to be a carrier by prenatal mutation analysis and carried to term. Conclusion We recommend uncultured chorionic villi for reliable prenatal enzymatic diagnosis of various lysosomal storage disorders on account of the low rate of false positive (0.5%) and false negative (2.2%) results. © 2015 John Wiley & Sons, Ltd.

Maple syrup urine disease (MSUD) is caused by mutations in genes BCKDHA, BCKDHB, DBT encoding E1α, E1β, and E2 subunits of enzyme complex, branched-chain alpha-ketoacid dehydrogenase (BCKDH). BCKDH participates in catabolism of branched-chain amino acids (BCAAs) - leucine, isoleucine and valine in the energy production pathway. Deficiency or defect in the enzyme complex causes accumulation of BCAAs and keto-acids leading to toxicity. Twenty-four patients with MSUD were enrolled in the study for molecular characterization and genotype-phenotype correlation. Molecular studies were carried out by sequencing of the 3 genes by Sanger method. Bioinformatics tools were employed to classify novel variations into pathogenic or benign. The predicted effects of novel changes on protein structure were elucidated by 3D modeling. Mutations were detected in 22 of 24 patients (11, 7 and 4 in BCKDHB, BCKDHA and DBT genes, respectively). Twenty mutations including 11 novel mutations were identified. Protein modeling in novel mutations showed alteration of structure and function of these subunits. Mutations, c.1065 delT (BCKDHB gene) and c.939G > C (DBT gene) were noted to be recurrent, identified in 6 of 22 alleles and 5 of 8 alleles, respectively. Two-third patients were of neonatal classical phenotype (16 of 24). BCKDHB gene mutations were present in 10 of these 16 patients. Prenatal diagnoses were performed in 4 families. Consanguinity was noted in 37.5% families. Although no obvious genotype-phenotype correlation could be found in our study, most cases with mutation in BCKDHB gene presented in neonatal period. Large number of novel mutations underlines the heterogeneity and distinctness of gene pool from India.

Nature inspired computing techniques has become a very popular topic in recent years. Number of applications in computer networks, robotics, biology, combinatorial optimization, etc. can be seen in literatures which are based on the bio-inspired techniques. Nature inspired techniques are proven to solve complex optimization problems irrespective of their problem size. This review summarizes various nature inspired migration algorithms and comparison between them, based on the automated tools, evolutionary techniques and applications.

Background The advancements in laboratory technology and knowledge of the mechanisms behind metabolic disorders have facilitated accurate and reliable laboratory testing in screening, diagnosis and treatment of inherited metabolic disorders. Therefore, quality assurance and improvement in diagnostic proficiency have become essential in this area. In most developing countries, standard practices for quality assurance in testing of enzymes, hormones and metabolites involved in these genetic disorders have not been fully implemented. We highlight the benefits of quality assurance and aim to create awareness for greater compliance with the criteria established for quality control to ensure accuracy in biochemical genetic testing. Methods Establishing the limit of detection and testing range for each analyte and enzyme are useful as a reference while setting up new assays. To minimize error, %CV should be monitored regularly. Evaluation of proficiency testing performance provides scope to the laboratory for improving testing quality. Results Low precision seen in lysosomal enzyme assays does not undermine their diagnostic efficacy as differentiation between patients and normal subjects is possible by setting % coefficient of variation cutoffs. Conclusions The study will facilitate the collaboration with other screening and diagnostic systems and help in development of new laboratory standards.

After a review of the current health scene in India, the authors suggest that the Government of India should consider seriously, the introduction of new born screening. As a first step, a central advisory committee should be constituted to recommend what is required to be done to strengthen the infrastructure and the manpower to carry out new born screening, and the disorders to be screened. In the urban hospitals newborn screening (NBS) for three disorders can be easily introduced (congenital hypothyroidism, congenital adrenal hyperplasia and G-6-PD deficiency), while in the rural areas this should begin with congenital hypothyroidism, especially in the sub Himalayan areas. Concurrently, logistic issues regarding diets and special therapies for inborn errors of metabolism should be sorted out, laboratories to confirm the diagnosis should be set up, and a cadre of metabolic physicians should be build up to treat those identified to have inborn errors of metabolism. Once these are established on a firm footing, tandem mass spectrometry should be introduced as it allows the identification of a number of disorders in an affordable manner. The recent improvements and current trends in health care in India have created the necessary infrastructure for adopting NBS for the benefit of infants in India.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a significant phenotypic variability in progression of the disease. Vascular endothelial growth factor (VEGF) has been reported to play a major role in renal pathophysiology. The aim of the present case-control study was to evaluate the association of two promoter polymorphisms (-2578C>A and-1154G>A) of VEGF gene and ADPKD. Genotyping was carried out in 123 ADPKD patients and 100 healthy controls, using a polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). The genotype, allele and haplotype frequencies of these two polymorphisms in ADPKD patients were compared with those in controls, as well as in patients with early and advanced chronic kidney disease (CKD) stages, using Chi-square (χ2) test. The distribution frequency of CC, CA and AA genotypes of -2578C>A polymorphism differed significantly between patients and controls (0.31, 0.63 and 0.06 vs 0.37, 0.44 and 0.19, respectively (P=0.003)), but no significantly different genotype distribution was observed for the-1154G>A polymorphism. The A allele of -2578C>A and G allele of -1154G>A, were significantly more present in the controls as compared to the patients, and may provide protection for CKD under recessive (OR, 3.73; 95% CI, 1.45-9.62; P=0.0042), and dominant (OR, 0.55; 95%CI, 0.31-0.98; P=0.041) models. The [A;G] haplotype was more frequently present in controls (18%) than in cases (8%), (OR 0.398; 95% CI 0.22-0.71; P=0.002). These results suggest that the two promoter polymorphisms of VEGF may modify the disease risk in ADPKD patients from North India.

Prenatal enzymatic diagnosis for an array of lysosomal storage disorders (LSDs) can be performed accurately, provided that a confirmed diagnosis by biochemical/molecular study in the index case is available and a strict defined protocol, specific to each individual disorder is followed. The present chapter describes the protocols for reliable and accurate prenatal enzymatic diagnoses by fluorometric and spectrophotometric methods of lysosomal storage disorders: Gaucher, Fabry, Pompe, Niemann Pick A/B, Tay Sach, Sandhoff, GM1, Mucoplysaccharidoses, Wolman, Krabbe, Metachromatic leukodystrophy, and Batten diseases using uncultured chorionic villi samples. The biological reference intervals for enzyme levels in normal and affected fetuses are given for interpretation of prenatal results. It is imperative to establish normal reference interval in each laboratory to take into account the local environment, technical variations, and different ethnicities. Besides, enzyme activity in the fetus should be represented as percentage of the mean activity of enzyme of normal fetuses. The pitfalls and challenges in prenatal diagnosis as well as technical problems in performing enzyme assays are also discussed to help the reader in standardization and performing the assays for correct diagnosis.

Prenatal enzymatic diagnosis for an array of lysosomal storage disorders (LSDs) can be performed accurately, provided that a confirmed diagnosis by biochemical/molecular study in the index case is available and a strict defined protocol, specific to each individual disorder is followed. The present chapter describes the protocols for reliable and accurate prenatal enzymatic diagnoses by fluorometric and spectrophotometric methods of lysosomal storage disorders: Gaucher, Fabry, Pompe, Niemann Pick A/B, Tay Sach, Sandhoff, GM1, Mucoplysaccharidoses, Wolman, Krabbe, Metachromatic leukodystrophy, and Batten diseases using uncultured chorionic villi samples. The biological reference intervals for enzyme levels in normal and affected fetuses are given for interpretation of prenatal results. It is imperative to establish normal reference interval in each laboratory to take into account the local environment, technical variations, and different ethnicities. Besides, enzyme activity in the fetus should be represented as percentage of the mean activity of enzyme of normal fetuses. The pitfalls and challenges in prenatal diagnosis as well as technical problems in performing enzyme assays are also discussed to help the reader in standardization and performing the assays for correct diagnosis.

Background : Sepsis is one of the most common causes of morbidity and mortality in the newborn. Early diagnosis and treatment is vital to improve outcome. The present study was therefore carried out to determine the usefulness of C-reactive protein (CRP) for evaluation of neonatal sepsis in teaching hospital of central India. Method: 82 neonates with clinical suspicion of sepsis were prospectively studied over a 12 month period. Blood was obtained from each subject recruited for the qualitative estimation of CRP. Blood culture was used as gold standard for diagnosis of NNS. Results: Of 82 neonates studied, 67 (81.7%) had positive CRP while 58 (70.73%) had positive blood culture. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of CRP were 81.7%, 88.0%, 95.7%, 59.5% and 83.2%. respectively. Conclusion : The qualitative method of estimating CRP which is cheap and rapid has moderate sensitivity, specificity and negative predictive value. It is a good diagnostic test and can identify the infection in neonates at the time of initial assessment.

Introduction: Tuberculosis as a disease is of great public health problem in developing countries like India. Children contribute a significant proportion of disease burden and suffer from severe form of disease, but because of difficulty in establishing an accurate diagnosis, data of disease burden in pediatric population is lacking. This study is an attempt to assess clinical profile of tuberculosis in children upto 5 years of age. Method: present study was conducted at Kamla Raja Hospital & Gajra Raja Medical College Gwalior over a period of six months. 77 cases up to 5 years of age were selected from in-patient department, who were diagnosed to have tuberculosis. A detailed history of epidemiological factors including past history of infectious disease, history of contact contributing to disease state was recorded on predesigned Performa. Complete clinical examination and laboratory investigation was done to confirm the diagnosis. Result: approximately 70 % of study group was distributed in 2- 5 years of age group. Cases of CNS tuberculosis formed the main bulk to the study contributing 70.13% followed by intrathoracic (~16.88%), disseminated (6.49%), abdominal (5.19%) & lymphoid (1.29%) tuberculosis. Severe malnutrition, low socio economic status, illiteracy of parents were the important epidemiological factor affecting the disease status of child. Conclusion: childhood tuberculosis remained the neglected part in NTCP until RNTCP was introduced. Childhood cases have shown increasing trends with the advent of HIV infection. Prompt suspicion and early diagnosis can be an important step in controlling this epidemic.

Objective-To study the adverse drug reactions in paediatric age group in a tertiary care hospital. Methods-A retrospective study was undertaken to analyse adverse drug events in paediatric department of a tertiary care hospital.Medical record sheets were analysed and adverse event marked as ADR by the paediatrician was included in the study. Causality, preventability and severity were analysed by 2 Pharmacologists. Other parameters like male to female ratio, most common class of drug causing ADR, common types of ADRs, commonly involved systems, polypharmacy were studied. Results64 cases of ADRs were identified in study duration(overall incidence 4.4%) of which 56% were females and infants the commonest age group. Antinfectives were the commonest drug class(68%) causing ADRs,with skin the commonest involved organ. 81% of ADRs were of moderate degree as compared to 1% of severe degree.76% cases fell in probable category of preventability where as 3% were definitely preventable.76.5% cases scored into probable category according to Naranjo’s scale of causality assessment. 86% cases were prescribed polypharmacy. ConclusionIncidence of Iatrogenic harm is rising and due to suboptimal ADR reporting practices only the tip of iceberg is seen. Though more vulnerable, paediatric age group is neglected in various aspects. To ensure safety we need to judiciously use drugs, strengthen ADR reporting and conduct more studies & awareness programmes.

Introduction: The Present study is an attempt to assess the level of lead in blood in general population and it’s Impact on intelligence. Methods: A random sample of 70 children between the ages of 1-12 year’s residing in and around Gwalior region, attending Pediatrics OPD of GRMC Gwalior, constituted the material for study. A detail history and examination was done to asses various factor affecting lead status of child. Blood lead level was assessed at DRDE Gwalior and Intelligence was also assessed simultaneously. Results: On data analysis more than 50% off study group was found to have blood lead level above safe level (10 mcg/dl). On analysis of effect of raised lead level on intelligence, it was found that raised blood lead level was associated with decrease in IQ. At various lead levels IQ status were as following, at lead level of 0 - 5 mcg/dl; IQ 96.64%, 5 - 10 mcg/dl; IQ 94.33%, 10 - 15 mcg/dl; IQ 89.05%, 15-20 mcg/dl; IQ 79.75% and at lead level more than 20 mcg/dl; IQ 73.8%. This decrease in intelligence level with increase in blood lead level was statically significant. Conclusion: A healthy appearing child may have silent lead poisoning affecting his intelligence without clinically apparent symptoms and signs until much later in life. High degree of suspicion, in a child with history of pica and poor nutrition status should be there for early diagnosis.

To determine the diagnostic accuracy of preeclampsia (PE) screening test offered in early pregnancy for the prediction of the risks for early-onset (requiring delivery32 weeks gestation) and late-onset (requiring delivery ≥32 weeks gestation) disease.In a retrospective study of 615 women with singleton pregnancy, the risk for PE was calculated by the combined effect of multiple variables: serum placental growth factor (PLGF) and pregnancy-associated plasma protein-A (PAPP-A), maternal age, parity, ethnicity, mean arterial pressure (MAP), body mass index (BMI), uterine artery-pulsatility index, and previous history of PE or hypertension (HT). The results of the screening test in three different groups of women were validated by pregnancy outcome: (i) control group - without any history of PE/HT; (ii) history of PE without HT; and (iii) history of HT without PE. The performance of the screening test was evaluated for early- and late-onset PE.The multivariate screening effectively identified cases of PE with97% specificity. The detection rate (DR) was 93.8% for late-onset PE at a false positive rate (FPR) of 2.3% and 44.4% for early-onset PE at an FPR of 0.0%. The incidence of PE was 7% overall, with 1.52% and 5.43% for early- and late-onset PE, respectively.The study demonstrated 96.6% diagnostic accuracy of the multi-variable screening test to predict the risk of PE in the first trimester. The negative predictive value (98%) reinforces the utility of cost-effective noninvasive screening test for the early detection of PE.PLGF: Placental growth factor; PAPP-A: Pregnancy-associated plasma protein-A; free β-HCG: Free beta-human chorionic gonadotropin; BMI: Body mass index; MAP: Mean arterial blood pressure; Ut-PI: Mean uterine artery pressure (left and right uterine artery)-pulsatility index; MoM: Multiple of median; NICE: National Institute for Health and Clinical Excellence.

High consanguinity rates, poor access to accurate diagnostic tests, and costly therapies are the main causes of increased burden of lysosomal storage disorders (LSDs) in developing countries. Therefore, there is a major unmet need for accurate and economical diagnostic tests to facilitate diagnosis and consideration of therapies before irreversible complications occur. In cross-country study, we utilized dried blood spots (DBS) of 1,033 patients clinically suspected to harbor LSDs for enzymatic diagnosis using modified fluorometric assays from March 2013 through May 2015. Results were validated by demonstrating reproducibility, testing in different sample types (leukocytes/plasma/skin fibroblast), mutation study, or measuring specific biomarkers. Thirty percent (307/1,033) were confirmed to have one of the LSDs tested. Reference intervals established unambiguously identified affected patients. Correlation of DBS results with other biological samples (n = 172) and mutation studies (n = 74) demonstrated 100% concordance in Gaucher, Fabry, Tay Sachs, Sandhoff, Niemann-Pick, GM1, Neuronal ceroid lipofuscinosis (NCL), Fucosidosis, Mannosidosis, Mucopolysaccharidosis (MPS) II, IIIb, IVa, VI, VII, and I-Cell diseases, and 91.4% and 88% concordance in Pompe and MPS-I, respectively. Gaucher and Pompe are the most common LSDs in India and Pakistan, followed by MPS-I in both India and Sri Lanka. Study demonstrates utility of DBS for reliable diagnosis of LSDs. Diagnostic accuracy (97.6%) confirms veracity of enzyme assays. Adoption of DBS will overcome significant hurdles in blood sample transportation from remote regions. DBS enzymatic and molecular diagnosis should become the standard of care for LSDs to make timely diagnosis, develop personalized treatment/monitoring plan, and facilitate genetic counseling.

Objective: The phenotype of systemic lupus erythematosus (SLE) in Asian Indians is more severe as compared with that in Caucasians. The reason is not clear. In this context, we studied serum levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4) and interlekin-10 (IL-10). Their interrelations and correlation with SLEDAI scores were evaluated. Materials and methods: Forty patients with active SLE and 40 controls were studied. The mean SLEDAI score and anti-ds DNA level of the patients were 21.45 ± 8.61 and 176.68 ± 81.31 (IU/ml), respectively. Cytokines were estimated by enzyme-linked immunosorbent assay. Results: In controls, the levels of IFN-γ were highest, followed by TNF-α, IL-10 & IL-4. In patients, however, the levels of TNF-α were highest, followed by IFN-γ, IL-10 & IL-4. IL-10 and IL-4 correlated negatively, and IFN-γ and TNF-α correlated positively with the SLEDAI scores. As compared with controls, in patients, the mean values of TNF-α, IL-10 and TNF-α/IL-10 ratio were higher by 6.9, 2.9 and 2.3 times, respectively ( p

Background: Neonatal mortality rate contributes significantly to under five mortality rates. Data obtained from pattern of admission and outcome may uncover various aspects and may contribute and help in managing resources, infrastructure, skilled hands for better outcome in future.Methods: This retrospective study was done on 1424 neonates who were admitted at LN Medical College and JK Hospital, Bhopal in neonatal intensive care unit (NICU) in the Department of Paediatrics from January 2013-December 2017.Results: 1424 newborns admitted within 24 hours of birth were included in the study. About 767 were male neonates, (Male: female1.16:1). The low birth weight babies were 54% in our study. Among the various causes of NICU admission, Respiratory distress was present in 555 (39%) of neonates, Respiratory distress syndrome (Hyaline membrane disease) being the most common cause of respiratory distress. Neonatal sepsis accounted for morbidity in 24% of neonates, with Klebsiella being the most common organism grown in the blood culture. The incidence of congenital anomalies was 2.5%. The neonatal mortality was found to be 11% in our study. Prematurity with Respiratory distress syndrome (Hyaline membrane disease) and perinatal asphyxia were the two most common causes of neonatal mortality in the study. Extremely low birth weight neonates had the highest case fatality rate in the study, which indicates the need to develop an efficient group of professionals in teaching hospitals who will provide highly specialized and focused care to this cohort of vulnerable neonates.Conclusions: Present study has shown respiratory distress, perinatal asphyxia, and sepsis as the predominant causes of neonatal morbidity. All three are preventable causes, and our health-care programs should be directed toward addressing the risk factors in the community responsible for the development of these three morbidities. The preterm and low birth weight babies had significantly high mortality even with standard intensive care; therefore, a strong and effective antenatal program with extensive coverage of all pregnant females specifically in outreach areas should be developed which will help in decreasing preterm deliveries and also lower the incidence of low birth weight babies.

To offer accurate prenatal diagnosis of lysosomal storage disorders in early pregnancy.Prenatal enzymatic diagnoses of Gaucher, Fabry, Pompe, Niemann Pick A/B, Tay Sach, Sandoff, GM1, mucoplysaccharidoses, Wolman, Krabbe, Metachromatic leukodystrophy and Batten diseases were made in uncultured chorionic villi samples by fluorometric/spectrophotometric methods.Of 331 prenatal enzymatic diagnosis, 207 fetuses (67%) were normal and 124 (37%) were affected. The interpretation of affected, normal and carrier fetuses was done using their respective reference ranges as well as % enzyme activity of normal mean. The prenatal molecular confirmation was feasible in 43 biochemically diagnosed fetuses. Of the 207 normal reported fetuses, post natal enzymatic confirmation was done in 23 babies, clinical status of another 165 babies was assessed as unaffected via questionnaire on telephone and 19 were lost to follow-up. In affected pregnancies, 123 opted for termination of which 44 were confirmed enzymatically after abortion. A single false positive was determined to be a carrier by prenatal mutation analysis and carried to term.We recommend uncultured chorionic villi for reliable prenatal enzymatic diagnosis of various lysosomal storage disorders on account of the low rate of false positive (0.5%) and false negative (2.2%) results.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of a broad spectrum of autoantibodies against nuclear, cytoplasmic and cell surface antigens and immune complex overload. Complement receptor 1 (CR1, CD 35), a transmembrane glycoprotein found on the surface of erythrocytes, leukocytes and glomerular podocytes plays a key role in the clearance of immune complexes and regulation of complement cascade. A drastic decline in the level of cell surface CR1 appears to be an important event in pathology of SLE. However, the etiology of lower than normal expression of cell surface CR1 in this disease is poorly understood. We studied the level of leukocyte CR1 transcription in 30 patients with active SLE and 30 controls by reverse transcriptase-polymerase chain reaction (RT-PCR) and related the same with the level of CR1 protein expression monitored by Western blotting. For RT-PCR, ratio of CR1/beta-actin was considered for semiquantitation of the level of CR1 transcription. Despite individual variation at the level of transcription, 70% (21 out of 30) of the patients expressed CR1 transcript at the lowest range of 0-15% as compared to the controls wherein only 30% (9 out of 30 individuals) demonstrated CR1 transcript in this range. Majority of the controls (70%) expressed CR1 transcript at the level above 15%. Mean level of CR1 transcript in patients (mean +/- S.D. = 21.09 +/- 14.3) was significantly lower than the controls (mean +/- S.D. = 48.91 +/- 26.34) (P0.001). The level of CR1 transcription correlated inversely with circulating immune complexes (CIC) (r = 0.52, P0.01). This may suggest that although erythrocyte CR1 is the chief vehicle for CIC clearance, drastic decline in leukocyte CR1 expression may impair the phagocyte mediated immune complex clearance and contribute to increased complement consumption in SLE. Total leukocyte CR1 protein expression was also significantly reduced in patients (P0.001) as compared to controls. This decline at the protein level gave a very significant positive correlation with CR1 transcript (r = 0.67, P0.01). A marginal increase in soluble CR1 (sCR1) was observed in the plasma (ELISA) of SLE patients compared to the controls but was insignificant. This paper for the first time brings evidence to suggest that reduced synthesis of CR1 contributes substantially to the low cell surface CR1 expression in SLE. Our findings also suggest increased proteolytic cleavage of leukocyte cell surface CR1 in these patients. However, evidence for the latter is indirect.

Background:Fusarium solani (FS) is an important source of fungal allergen. A 45-kD major allergen of FS showed reactivity with patients’ sera sensitive to many fungi. Objectives: To purify and characterize a 45-kD common allergenic protein from FS, which may be useful for the diagnosis of and therapy for fungal allergy. Methods: FS culture filtrate extract was separated on SDS-PAGE; 45-kD protein was electroeluted and purified on C18 column using reverse-phase high-pressure liquid chromatography (rpHPLC). The purified protein was functionally and biochemically characterized by in vitro and in vivo methods. Results: The 45-kD protein showed a single peak on rpHPLC. The N-terminal amino acid sequence of this protein did not show homology to enolase or known fungal proteins. It showed cross-reactivity with Epicoccum nigrum, Curvularia lunata, Cladosporium herbarum and Alternaria alternata by ELISA and ELISA inhibition using rabbit antibodies raised against these fungi. IgE ELISA inhibition with patients’ sera positive to different fungi demonstrated allergenic cross-reactivity of the 45-kD protein with other fungal extracts. This 45-kD protein released a significant amount of histamine in FS-allergic patients. Conclusion: A cross-reactive 45-kD allergenic/antigenic protein was purified to homogeneity and characterized. It has prospects for use in allergen therapy.

Background: Grass pollens are known to induce type I allergic reactions in a large number of genetically predisposed individuals. Earlier studies have recognized Imperata cylindrica (Ic) pollen as an important source of aeroallergen which contained 7 IgE binding proteins in the MW range of 85–16 kD. Objectives: To isolate, purify and characterize a cross-reactive allergenic protein from Ic pollen extract for diagnosis and therapy of grass pollen allergy. Methodology: Ic pollen extract was fractionated using DEAE Sephadex A-50, Sephadex G-200 and Mono Q column. Allergenic activity of the fractions was checked by ELISA, skin tests, ELISA inhibition and immunoblot using sera of Ic-sensitive patients. A 67-kD protein was purified to homogeneity from Ic-VIII. The allergenic determinants of this protein were identified by SDS-PAGE and immunoblot after CNBr treatment. Results: Among Ic fractions, Ic-VIII was highly potent by ELISA, skin tests and showed cross-reactivity with 4 other tropical grasses by immunoblot and ELISA inhibition. The subfraction Ic-VIIIe1 of Ic-VIII showed a band at 67 kD on SDS-PAGE. On CNBr treatment, it gave 7 peptides, 3 of which were found to be allergenic. Conclusion: A 67-kD protein (Ic-VIIIe1) was isolated, purified to homogeneity and partially characterized. It showed cross-reactivity with tropical grasses tested and contained at least three allergenic determinants.

Putranjiva roxburghii (PR) pollen has been found to be an important aeroallergen for type I hypersensitivity. In the present study, the IgE binding proteins of PR pollen have been c